Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies

ABSTRACT Synapses represent an important target of Alzheimer disease (AD), and alterations of their excitability are among the earliest changes associated with AD development. Synaptic activation has been shown to be protective in models of AD, and deep brain stimulation (DBS), a surgical strategy that modulates neuronal activity to treat neurological and psychiatric disorders, produced positive effects in AD patients. However, the molecular mechanisms underlying the protective role(s) of brain stimulation are still elusive. We have previously demonstrated that induction of synaptic activity exerts protection in mouse models of AD and frontotemporal dementia (FTD) by enhancing the macroautophagy/autophagy flux and lysosomal degradation of pathological MAPT/Tau. We now provide evidence that TFEB (transcription factor EB), a master regulator of lysosomal biogenesis and autophagy, is a key mediator of this cellular response. In cultured primary neurons from FTD-transgenic mice, synaptic stimulation inhibits MTORC1 signaling, thus promoting nuclear translocation of TFEB, which, in turn, induces clearance of MAPT/Tau oligomers. Conversely, synaptic activation fails to promote clearance of toxic MAPT/Tau in neurons expressing constitutively active RRAG GTPases, which sequester TFEB in the cytosol, or upon TFEB depletion. Activation of TFEB is also confirmed in vivo in DBS-stimulated AD mice. We also demonstrate that DBS reduces pathological MAPT/Tau and promotes neuroprotection in Parkinson disease patients with tauopathy. Altogether our findings indicate that stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau. This mechanism, underlying the protective effect of DBS, provides encouraging support for the use of synaptic stimulation as a therapeutic treatment against tauopathies.Abbreviations: 3xTg-AD: triple transgenic AD mice; AD: Alzheimer disease; CSA: cyclosporine A; DBS: deep brain stimulation; DIV: days in vitro; EC: entorhinal cortex; FTD: frontotemporal dementia; gLTP: glycine-induced long-term potentiation; GPi: internal segment of the globus pallidus; PD: Parkinson disease; STN: subthalamic nucleus; TFEB: transcription factor EB
Prediction of right ventricular failure after left ventricular assist device implantation: role of vasodilator challenge.

AIMS Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve. METHODS AND RESULTS Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481-0.871; P = 0.004), pulmonary artery systolic pressure (PASP) (OR: 0.856, CI: 0.761-0.964; P = 0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073-0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033). CONCLUSION Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.
Prospects for developing efficient targets for the xenomonitoring and control of Simulium damnosum s.l., the major vectors of onchocerciasis in Africa

Despite the ethical issues concerning the continued use of Human Landing Catches (HLC) to monitor the Simulium damnosum complex for epidemiological monitoring of onchocericasis, few attempts to develop alternatives have been reported. In studies on a wild population of S. damnosum in Burkina Faso, we tested visual targets (different sizes and shapes) and olfactory stimuli (CO2, and POCA and BG‐lure® odour blends) for their ability to attract and collect host seeking blackflies. At each trap, blackflies were caught with appropriately sized electrocuting grids and results from Latin square design tests were compared. Throughout, HLCs captured more blackflies than the targets. Of the traps tested, small targets (0.0625 and 0.5 m2) were the most efficient visual lure in terms of the number of S. damnosum captured per unit area 1.7–5× more than larger targets. Overall, results suggested that sticky black targets of horizontal rectangular shape (0.125–0.5 m2) and baited with a POCA and/or CO2 mixture could provide a cheap practical field alternative to HLC for onchocerciasis xenomonitoring, subject to confirmation that the design has no inherent bias for certain members of the S. damnosum species complex.
An Augmented Reality–Based Guide for Mechanical Ventilator Setup: Prospective Randomized Pilot Trial

Background Recently, the demand for mechanical ventilation (MV) has increased with the COVID-19 pandemic; however, the conventional approaches to MV training are resource intensive and require on-site training. Consequently, the need for independent learning platforms with remote assistance in institutions without resources has surged. Objective This study aimed to determine the feasibility and effectiveness of an augmented reality (AR)–based self-learning platform for novices to set up a ventilator without on-site assistance. Methods This prospective randomized controlled pilot study was conducted at Samsung Medical Center, Korea, from January to February 2022. Nurses with no prior experience of MV or AR were enrolled. We randomized the participants into 2 groups: manual and AR groups. Participants in the manual group used a printed manual and made a phone call for assistance, whereas participants in the AR group were guided by AR-based instructions and requested assistance with the head-mounted display. We compared the overall score of the procedure, required level of assistance, and user experience between the groups. Results In total, 30 participants completed the entire procedure with or without remote assistance. Fewer participants requested assistance in the AR group compared to the manual group (7/15, 47.7% vs 14/15, 93.3%; P=.02). The number of steps that required assistance was also lower in the AR group compared to the manual group (n=13 vs n=33; P=.004). The AR group had a higher rating in predeveloped questions for confidence (median 3, IQR 2.50-4.00 vs median 2, IQR 2.00-3.00; P=.01), suitability of method (median 4, IQR 4.00-5.00 vs median 3, IQR 3.00-3.50; P=.01), and whether they intended to recommend AR systems to others (median 4, IQR 3.00-5.00 vs median 3, IQR 2.00-3.00; P=.002). Conclusions AR-based instructions to set up a mechanical ventilator were feasible for novices who had no prior experience with MV or AR. Additionally, participants in the AR group required less assistance compared with those in the manual group, resulting in higher confidence after training. Trial Registration ClinicalTrials.gov NCT05446896; https://beta.clinicaltrials. gov/study/NCT05446896
Protein-bound polysaccharide K prolonged overall survival in gastric cancer patients from a non-Japanese Asian country who received gastrectomy and adjuvant chemotherapy

Adding protein-bound polysaccharide K (PSK) to adjuvant chemotherapy with mitomycin and fluorouracil after gastrectomy for gastric cancer was demonstrated to improve survival in a previous study in Japan. However, the efficacy of PSK outside Japan and in combination with other adjuvant chemotherapeutic agents remains unclear. The aims of this study were to evaluate the efficacy of PSK. We conducted a population-based historical cohort study using the National Health Insurance Research Database of Taiwan. We performed sensitivity analysis with propensity score matching to control for possible confounders. Patients who used PSK (PSK group) were matched at a 1:4 ratio to those who had never used PSK (control group) after adjusting for covariates including sex, age, urbanization, income and comorbidities. The primary outcome was overall survival. Multivariate hazard ratios from competing risk analysis were calculated by adjusting for demographic data and all confounding factors. From 1999 to 2008, we identified 10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed after propensity score matching. The median overall survival was 6.49 years (95% confidence interval [CI] 5.22–7.63) in the PSK group and 3.59 years (95% CI 3.38–3.80) in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival (hazard ratio 0.76, P < .0001). Adjuvant chemotherapy combined with PSK significantly prolonged overall survival in gastric cancer patients after gastrectomy.
Estimation of liquid sterilization using critical voltage under high electric field pulses

Our article compared the survival ratio obtained using experiments with that calculated using a sterilization mechanism model. We applied high‐voltage pulses to Escherichia coli in 1 × 10−3 mol/l NaCl aqueous solutions and estimated the survival ratio in a model of high electric field pulse sterilization. The results show that the survival ratios of E. coli decrease with increasing number of pulses, electric field intensity, pulse width, and sample temperature. The experimental results for the survival ratio showed good agreement with values calculated using the sterilization mechanism model. Our study shows that the survival ratio of E. coli can be estimated using high electric field pulses. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury

Angiotensin-converting enzyme 2 (ACE2) is the carboxypeptidase to degrade angiotensin II (Ang II) to angiotensin 1–7 (Ang 1–7) and improves the pathologies of cardiovascular disease and acute respiratory distress syndrome (ARDS)/acute lung injury. B38-CAP is a bacteria-derived ACE2-like carboxypeptidase as potent as human ACE2 and ameliorates hypertension, heart failure and SARS-CoV-2-induced lung injury in mice. Recombinant B38-CAP is prepared with E. coli protein expression system more efficiently than recombinant soluble human ACE2. Here we show therapeutic effects of B38-CAP on abdominal sepsis- or acid aspiration-induced acute lung injury. ACE2 expression was downregulated in the lungs of mice with cecal ligation puncture (CLP)-induced sepsis or acid-induced lung injury thereby leading to upregulation of Ang II levels. Intraperitoneal injection of B38-CAP significantly decreased Ang II levels while upregulated angiotensin 1–7 levels. B38-CAP improved survival rate of the mice under sepsis. B38-CAP suppressed the pathologies of lung inflammation, improved lung dysfunction and downregulated elevated cytokine mRNA levels in the mice with acute lung injury. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for the patients with severe sepsis or ARDS.
Making a meaningful difference through collaboration: The experiences of healthcare staff redeployed to a contact tracing and monitoring team as part of the COVID-19 response

ABSTRACT During the coronavirus disease 2019 (COVID-19) pandemic, the health care system experienced unprecedented demands with many health care workers being redeployed. Although there are emerging studies investigating redeployment to acute care, the experience of redeployment to roles outside of these settings, such as to contact tracing and monitoring (CTM) teams, has not been reported. This research was designed to explore health care workers’ experience of redeployment to a regional COVID-19 CTM team. Staff redeployed to this CTM team completed an anonymous online survey following the second wave of the COVID-19 pandemic in Victoria, Australia. The survey used open-ended questions to explore participants’ perceptions of what did and did not work well during their redeployment. Inductive template thematic analysis of the data found that during their redeployment to CTM teams, participants experienced a sense of collaboration, the opportunity for professional growth, and the perception of making a meaningful contribution to the pandemic. Redeployed CTM team members also described a need to adapt to constant change and felt that the redeployment took a personal toll on them. The findings from this research may be useful to support preparedness of health care workers for redeployment in future complex or crisis situations.
Deep Learning and Imaging for the Orthopaedic Surgeon

➤ In the not-so-distant future, orthopaedic surgeons will be exposed to machines that begin to automatically “read” medical imaging studies using a technology called deep learning. ➤ Deep learning has demonstrated remarkable progress in the analysis of medical imaging across a range of modalities that are commonly used in orthopaedics, including radiographs, computed tomographic scans, and magnetic resonance imaging scans. ➤ There is a growing body of evidence showing clinical utility for deep learning in musculoskeletal radiography, as evidenced by studies that use deep learning to achieve an expert or near-expert level of performance for the identification and localization of fractures on radiographs. ➤ Deep learning is currently in the very early stages of entering the clinical setting, involving validation and proof-of-concept studies for automated medical image interpretation. ➤ The success of deep learning in the analysis of medical imaging has been propelling the field forward so rapidly that now is the time for surgeons to pause and understand how this technology works at a conceptual level, before (not after) the technology ends up in front of us and our patients. That is the purpose of this article.
Factors affecting production and effectiveness, performance improvement and mechanisms of action of bacteriocins as food preservative

Abstract Modern society is increasingly attracted with safe, natural, and additive-free food products, that gives preference to bacteriocins produced by General Recognized as Safe bacteria as a food preservative. Bacteriocins have been reported to be effective in extending shelf life of diverse foods such as meats, dairy products, wine, juice, and fruits and vegetables, whereas commercialized bacteriocins remain only nisin, pediocin, and Micocin. It is important that commercialized preservatives undergo an easy-to-handle manufacturing while maintaining high efficacy. Limited application of bacteriocins is most often caused by the absence of legislatives for use, low production, high cost and complicated purification process, reduced efficiency in the complex food matrix and insufficiently defined mechanism of action. Accordingly, this review provides an overview of bacteriocins, in relation to production stimulation, general purification scheme, impact of food matrix on bacteriocin effectiveness, and collaborative technology to improve bacteriocin performances. It is worth to note that purification and performance improvement technology remain the two challenging tasks in promoting bacteriocins as a widely used bio-preservative. Furthermore, this review for the first time divides bacteriocin receptors into specific classes (class I, II, III) and nonspecific class, to provide a basis for an in-depth understanding of the mechanism of action.
Development of localisation and mapping software for autonomous cars

Autonomous car requires localisation and mapping capabilities to model the surrounding environment and to plan a safe and efficient route for the autonomous driving. Implementation of the localisation and mapping software depends on the type of sensors, map formats, computing environment, and processing algorithms. These dependencies make it difficult to extend, reuse, and maintain localisation and mapping software. The common software platform and software development guideline is a way to address the software dependency issues and to enhance the software reusability, scalability, maintainability, and transferability. Therefore, this study proposes a common software platform and implementation guidelines for localisation and mapping of autonomous cars. The common software platform for localisation and mapping is built on the philosophy of the AUTomotive Open System Architecture (AUTOSAR), which is a standard automotive software platform. The software development methodology of AUTOSAR applies to implementation guidelines of the localisation and mapping software. A graph structure of localisation and mapping is used to design the common software platform. The proposed common software platform and design methodology are evaluated using practical applications of localisation and mapping in a real autonomous car. The results show that the proposed platform and methodology are able to improve the reusability, scalability, maintainability, and transferability of the localisation and mapping software.
Edinburgh Research Explorer Variable word rate N-grams

The rate of occurrence of words is not uniform but varies from document to document. Despite this observation, parameters for conventional n -gram language models are usually derived using the assumption of a constant word rate. In this paper we investigate the use of variable word rate assumption, modelled by a Poisson distribution or a continuous mixture of Poissons. We present an approach to estimating the relative frequencies of words or n - grams taking prior information of their occurrences into account. Discounting and smoothing schemes are also considered. Using the Broadcast News task, the approach demonstrates a reduction of perplexity up to 10%.
template segregation in differentiating embryonic stem cells.

Furthermore, our data support the hypothesis that retention of chromatids with the “old” template DNA pre-serves the epigenetic memory of cell fate, whereas localization of “new” DNA strands and de novo DNA methyltransferase to the lineage-destined daughter cell facilitates epigenetic adaptation to a new cell fate.
Amazon Echo: The Best User Guide to Master Amazon Echo Fast

Amazon Echo Sale price. You will save 66% with this offer. Please hurry up! The Best User Guide to Master Amazon Echo Fast (Alexa skills kit, users guide, Amazon Echo, web services, digital media, tips and tricks) The Amazon Echo is a device with personal assistant functions operated by voice commands. It uses the Alexa platform to connect with unlimited resources from the Alexa cloud. Echo users will be able to gain access to various information including, but not limited to, music and general information such as traffic and weather updates. In addition, users can also perform both office and home management through the device. Sadly, Amazon Echo doesnt come with a complete guide or handbook to help you unfold its full potential. With that in mind, this book was written to serve as an all-in-one guide to help both newbies and longtime users of Amazon Echo. Your Personal Echo Guide: The Ultimate Handbook for Amazon Echo features several chapters that will help you master the device even if you have zero experience. The chapters in this book are as follows: Basic Operations of Amazon Echo How to Setup and Use the Device Setting Up and Using Echo Skills The above chapters will take you to the necessary topics that will help you grasp the devices features without experiencing difficulties. In other words, it will serve as your guide in mastering virtual operations through the Alexa cloud. These operations also allow Amazon in identifying your common dose of information based on your previous voice commands. Without sufficient knowledge, you may find yourself lost with unanswered questions and misunderstood commands. This book will also enlighten you with regards to the privacy security of the device. Many people tend to overlook the devices benefits due to the fact that it is always listening. It appears to be a violation of peoples lives and this book aims to dwell on that topic as well. Download your copy of "Amazon Echo" by scrolling up and clicking "Buy Now With 1-Click" button. Tags: Amazon Echo, Amazon Echo Course, Amazon Echo Book, Amazon Echo User Guide, Amazon Echo Book-Course, Amazon Echo for Beginners, users guide, amazon echo benefits, voice command device, amazon device, home devices, alexa, alexa kit, Alexa Skills Kit, digital devices, smart device, multifunctional device, beginners guide, main functions, personal control, time management, business device, to-do lists, audiobooks, amazon prime, Alexa Voice Service, tips and tricks, Amazon Echo at home, Amazon Echo functions.