Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite

DMPS, a drug licensed to treat mercury poisoning, is preclinically effective as an oral therapeutic for treating certain hemotoxic snakebites. Biting back against snakebites Snakebite envenoming is a neglected tropical disease that causes numerous injuries and deaths worldwide. It is difficult to treat because antivenom is unaffordable, not accessible in remote areas, and specific for each individual type of snake. In search of readily available treatments, Albulescu et al. examined a selection of metal chelators that are approved for use in human patients. Treatment with DMPS, a derivative of dimercaprol, was effective against a variety of saw-scaled viper venoms in mouse models when given soon after exposure, suggesting its potential for repurposing as a prehospital treatment. A related Focus by Koh et al. discusses the implications of this study. Snakebite envenoming causes 138,000 deaths annually, and ~400,000 victims are left with permanent disabilities. Envenoming by saw-scaled vipers (Viperidae: Echis) leads to systemic hemorrhage and coagulopathy and represents a major cause of snakebite mortality and morbidity in Africa and Asia. The only specific treatment for snakebite, antivenom, has poor specificity and low affordability and must be administered in clinical settings because of its intravenous delivery and high rates of adverse reactions. This requirement results in major treatment delays in resource-poor regions and substantially affects patient outcomes after envenoming. Here, we investigated the value of metal ion chelators as prehospital therapeutics for snakebite. Among the tested chelators, dimercaprol (British anti-Lewisite) and its derivative 2,3-dimercapto-1-propanesulfonic acid (DMPS) were found to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. Moreover, DMPS prolonged or conferred complete survival in murine preclinical models of envenoming against a variety of saw-scaled viper venoms. DMPS also considerably extended survival in a “challenge and treat” model, where drug administration was delayed after venom injection and the oral administration of this chelator provided partial protection against envenoming. Last, the potential clinical scenario of early oral DMPS therapy combined with a delayed, intravenous dose of conventional antivenom provided prolonged protection against the lethal effects of envenoming in vivo. Our findings demonstrate that the safe and affordable repurposed metal chelator DMPS can effectively neutralize saw-scaled viper venoms in vitro and in vivo and highlight the promise of this drug as an early, prehospital, therapeutic intervention for hemotoxic snakebite envenoming.
Comparison between criteria for diagnosing malnutrition in patients with advanced chronic liver disease: GLIM group proposal versus different nutritional screening tools.

BACKGROUND Different nutritional screening instruments can be used to identify the risk of malnutrition in advanced chronic liver disease patients. The present study aimed to evaluate and compare two nutrition screening tools with the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria for malnutrition in patients with advanced chronic liver disease. METHODS Two nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002) and Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT), were assessed for 166 patients with liver cirrhosis. We compared medium/high nutritional risk screening with the diagnosis of malnutrition, using the GLIM criteria as the reference standard. RESULTS According to the GLIM criteria, 57.3% of the patients were malnourished. NRS and RFH-NPT identified, respectively, 36.1% and 52.4% of patients with nutritional risk. RFH-NPT presented better agreement with the diagnosis according to GLIM criteria (k = 0.64; 95% confidence interval = 0.52-0.75), higher sensitivity (80%), higher negative predictive value (79%) and larger area under the curve (82.3%) compared to the NRS. CONCLUSIONS RFH-NPT, when compared with the GLIM method, has substantial agreement in identifying nutritional risk, good sensitivity and good value for diagnosing malnutrition in patients with advanced chronic liver disease.
Catchments as Basic Units of Management in Conservation Biology Courses

ology have left the course with a wealth of knowledge and little practical ability. I therefore decided to discuss conservation practice and theory with university lecturers from three continents-South America, North America, and Australia-to understand where the gaps are between my conservation biology course and the practice of conservation biology in the field. The most obvious difference I found was between researchers who work in deserts and seas and those who work in other biomes. Desert research-
Fonctions physiologiques des canaux chlorure de la famille ClC

Le clonage d’un canal chlorure dans l’organe electrique de la torpille en 1990 a permis l’identification d’une vaste famille de canaux chlorure dont les representants sont exprimes aussi bien chez les bacteries que dans les plantes ou chez les mammiferes. Ces canaux, appeles ClC ou dependants du voltage, ont une distribution tis-sulaire tres variee et peuvent s’exprimer dans la membrane plasmique comme sur les membranes des organites intracellulaires. Leur decouverte recente fait que de nombreux aspects de l’organisation, des proprietes electrophysiologiques et des fonctions de ces canaux restent indetermines. Nous faisons le point dans cet article sur les donnees actuelles en insistant sur trois fonctions physiologiques principales : le controle de l’excitabilite musculaire, la participation a l’absorption de chlorure dans le tube renal et l’implication dans les phenomenes d’endocytose.
Temporal Changes in Allele Frequencies and a Population's History of Severe Bottlenecks

Monitoring temporal changes in genetic variation has been suggested as a means of determining if a population has experienced a demographic bottleneck. Simulations have shown that the variance in allele frequencies over time (F) can provide reasonable estimates of effective population size (Nc). This relationship between F and Ne suggests that changes in allele frequencies may provide a way to determine the severity of recent demographic bottlenecks experienced by a population. We examined allozyme variation in experimen- tal populations of the eastern mosquitofish (Gambusia holbrooki) to evaluate the relationship betuween the se- verity of demographic bottlenecks and temporal variation in allele frequencies. Estimates of F from both the fish populations and computer simulations were compared to expected rates of drift. We found that different methods for estimating F had little effect on the analysis. The variance in estimates of F uas large among both experimental and simulated populations experiencing similar demogrcaphic bottlenecks. Temporal changes in allele frequencies suggested that the experimental populations had experienced bottlenecks, but there was no relationship between observed and expected values of F. Futrthermore, genetic drift was likely to be underesti- mated in populations experiencing the most severe bottlenecks. The weak relationship between F and bottle- neck severity is probably due to both sampling error associated with the number of polymorphic loci exam- ined and the loss of alleles during the bottlenecks. For populations that may have experienced severe bottlenecks, caution should be used in making evolutionary interpretations or management recommenda- tions based on temporal changes in allele frequencies.
Efficacy and Safety of Continuous Paravertebral Block after Minimally Invasive Radical Esophagectomy for Esophageal Cancer

Objective To compare the effects of continuous paravertebral block analgesia and patient-controlled intravenous analgesia after minimally invasive radical esophagectomy for esophageal cancer and their effects on postoperative recovery. Methods A retrospective analysis was performed among 233 patients who underwent minimally invasive esophageal cancer radical operation and met the requirements, including 87 patients (group C) who were successfully placed with a continuous paravertebral block device under direct vision and 146 patients (group P) who used a patient-controlled intravenous analgesia device. Visual analogue pain score (VAS) at rest and in motion for 1, 3, 6, 12, 24, 36, and 48 hours after awakening, incidence of adverse reactions of the two analgesic methods, occurrence of pulmonary complications after operation, use of emergency analgesics, and hospital stay after operation was recorded. Results The VAS scores of group C in resting and active state at 1, 3, 6, 12, 24, 36, and 48 hours after operation were significantly lower than those of group P (P < 0.001). The incidence of adverse reactions, pulmonary complications, and the use of emergency analgesics in group C were lower than those in group P (P < 0.05). The hospitalization time of group C was significantly shortened, and the satisfaction degree of group C was significantly higher than that of group P (P < 0.05). Conclusion Paravertebral block is safe and effective for patients undergoing minimally invasive radical esophagectomy. The incidence of adverse reactions and complications is lower, and the satisfaction of postoperative analgesia is higher, which is beneficial to the rapid recovery of patients after operation.
Macrophage Activities in Myocardial Infarction and Heart Failure

Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.
Effect of bisphosphonates on the crystallization of stone-forming salts in synthetic urine

Purpose We investigated the inhibitory effect of bisphosphonates (BPs) on the crystallization of calcium oxalate monohydrate (COM), calcium phosphate (CaP), and magnesium ammonium phosphate (MAP) in synthetic urine, aiming to see 1) which specific BPs work best on a particular type of crystal and 2) what is the lowest concentration of BPs that inhibits crystal formation. Materials and Methods Crystals from synthetic urine were exposed to different concentrations of BPs. Urinary turbidity was used as a marker of crystallization and was measured by spectrophotometry by use of a validated method in our laboratory. The percent inhibitory activity (IA) was calculated by using the formula: (a−b )/a×100, where a is baseline maximal turbidity and b is maximal turbidity with various concentrations of medication. Potassium citrate and magnesium citrate were used as positive controls. Results At the lowest dose of 0.001 mg/mL, risedronate induced the highest IA of 37% on CaP, whereas ibandronate had the strongest IA on COM (24%). To initiate the inhibition of MAP crystallization, risedronate required a two-fold higher concentration (0.002 mg/mL) to reach 30% IA, whereas etidronate required a four-fold higher concentration (0.004 mg/mL) to reach 42% IA. Conclusions BPs are good inhibitors of crystallization in synthetic urine, with risedronate and ibandronate being the most potent. At a low clinically acceptable dose, their highest inhibitory action was on CaP and COM crystals. Higher doses were needed to prevent MAP crystallization. Further investigation of the use of BPs in kidney stone prevention is warranted.
CCL Design Improvements at SSC Linac

Many impbortant changes in CCL [l] beam dynamics and cavity geometry have been made recently. The new design will bring about a decrease in emittance growth in CCL from 50% to 10% and save of one klystron station. RF performance of the CCL has also been improved.
Augmenting Network Flows with User Interface Context to Inform Augmenting Network Flows with User Interface Context to Inform Access Control Decisions Access Control Decisions

Whitelisting IP addresses and hostnames allow organizations to employ a default-deny approach to network traﬃc. Organizations employing a default-deny approach can stop many malicious threats, even including zero-day attacks, because it only allows explicitly stated legitimate activities. However, creating a comprehensive whitelist for a default-deny approach is diﬃcult due to user-supplied destinations that can only be known at the time of usage. Whitelists, therefore, interfere with user experience by denying network traﬃc to user-supplied legitimate destinations. In this thesis, we focus on creating dynamic whitelists that are capable of allowing user-supplied network activity. We designed and built a system called Harbinger, which leverages user interface activity to provide contextual information in which network activity took place. We built Harbinger for Microsoft Windows operating systems and have tested its usability and eﬀectiveness on four popular Microsoft applications. We ﬁnd that Harbinger can reduce false positives-positive detection rates from 44%-54% to 0%-0.4% in IP and DNS whitelists. Furthermore, while traditional whitelists failed to detect propagation attacks, Harbinger detected the same attacks 96% of the time. We ﬁnd that our system only introduced six milliseconds of delay or less for 96% of network activity.
New Techniques of Image Denoising using Multiwavelet by Neighbor Mapping

The Image denoising naturally corrupted by noise is a classical problem in the field of signal or image processing. Denoising of a natural images corrupted by Gaussian noise using multi-wavelet techniques are very effective because of its ability to capture the energy of a signal in few energy transfer values. Multi-wavelet can satisfy with symmetry and asymmetry which are very important characteristics in signal processing. The better denoising result depends on the degree of the noise. Generally, its energy is distributed over low frequency band while both its noise and details are distributed over high frequency band. Corresponding hard threshold used in different scale high frequency sub-bands. In this paper proposed to indicate the suitability of different wavelet and multi-wavelet based and a size of different neighborhood on the performance of image Denoising algorithm in terms of PSNR value. Finally it's compare wavelet and multi-wavelet techniques and produced best denoised image using neighbor mapping and multiwavelet technique based on the performance of image denoising algorithm in terms of PSNR Values.
Including renewable electricity generation and CCS into the DART model

This paper describes how a variety of renewable electricity generation technologies (wind, hydro, solar, and solid biomass) and advanced electricity generation from coal and gas including carbon capture and storage (CCS) is included into the multi-region, multi-sector recursive dynamic CGE-model DART. In principle, the electricity sector are split into several generation technologies to allow for renewable electricity production. CCS is introduced as latent technology and is deployed only under a sufficiently high carbon price. In all technologies, a fixed resource is used to calibrate for the path of the generation technologies. ∗Kiel Institute for the World Economy, Hindenburgufer 66, 24105 Kiel, Germany; Telephone/Fax: +49(0)431-8814-580/502; Email: matthias.weitzel@ifw-kiel.de This note has been written as part of the POEM project (Policy Options to engage Emerging Asian economies in a post-Kyoto regime), co-funded by the European Commission DG Research and Innovation within the Seventh Framework Programme.
CONSUMER LOGISTICS IN HYPERMARKET AND ITS APPLICATION TO SMES IN MALAYSIA

The aim of this paper is to analyze consumer logistic amongst hypermarket customers in Malaysia and its implication to the SME grocers retailing subsector. The scope of this paper is to focus on the importance and the application of the consumer logistics concept around the Klang Valley. Among the elements of the consumer logistics discussed are 1) the scarcity of time, 2) selection of shopping location, 3) planned and impulse shopping and 4) brand switching with retailers are unable to stock up on preferred brands. Taking this result, this paper discusses on the possible application to SMEs in order to resolve the problem of moving products to the consumers. We found that certain consumer behaviour needs to be understood by the SME retailers in their business management. The operating hours, product quality and other services are important aspects of consumer logistics to be given high priority.
Children’s mental health: Is poverty the diagnosis?

The case of a 6-year-old boy who was referred to a physician by his school counselor for investigation of anxiety and possible attention deficit hyperactivity disorder illustrates the need to consider the role of poverty when addressing mental health concerns. After determining that income insecurity could be contributing to the boy’s symptoms, the physician used a poverty intervention tool to screen for the effects of poverty and make recommendations to prevent adverse health outcomes. Mental health and behavioral concerns are common in children and youth presenting with undifferentiated complaints in both pediatric and primary care settings. Psychiatric disorders are frequently multifactorial and require a comprehensive assessment of the patient’s environmental context, including the family’s socioeconomic status. Poverty is a risk factor for mental health conditions in childhood and is associated with lower academic achievement and impaired cognitive development secondary to direct effects on the developing hypothalamic-pituitary-adrenal axis and indirect effects on a child’s environment. British Columbia’s childhood poverty rate is well above the national average and is compounded by significant unmet core housing need and widening provincial income disparity. We recommend screening for poverty with office-based interventions and accounting for income insecurity in all mental health diagnoses and treatment plans. We also strongly recommend implementing a national poverty reduction strategy to address social determinants of health in the early years and improve the health of future generations. Case data A 6-year-old boy was referred for assessment and treatment recommendations by his school counselor because of anxiety, school difficulties, and possible attention deficit hyperactivity disorder (ADHD). The boy was from a two-parent family and had a 14-year-old brother. Both parents were employed, the father as a cargo delivery driver and the mother in a hospital cafeteria. The boy’s mother had started shift work 6 months previously and was working 6 days a week so that the family could meet increasing rent costs. They lived in a small two-bedroom apartment and the boy slept on the pull-out couch in the living room because his 14-year-old brother demanded privaDr Jakovljevic is a PGY-5 resident in the Department of Psychiatry at the University of British Columbia. Dr Miller is an assistant professor in the Department of Psychiatry at UBC and a child and adolescent psychiatrist at BC Children’s Hospital and Vancouver Community Mental Health Services. Dr Fitzgerald is a developmental pediatrician at Sunny Hill Health Centre for Children. She is also medical director of Alderwood Family Development Centre and a clinical associate professor in the Department of Pediatrics at UBC. This article has been peer reviewed.
Comparison of ultrasound and electrical neurostimulation guidance in axillary brachial plexus block

Objectives: To compare ultrasound guidance (USG) and electrical neurostimulation guidance (ENSG) in axillary brachial plexus block in terms of block performing time, sensory and motor block quality, and patient satisfaction. Methodology: 200 patients undergoing elective carpal tunnel syndrome surgery were randomly assigned to one of two groups equally; the USG group or the ENSG group. Axillary blocks were performed with a mixture of 15 ml of lidocaine 2% and 15 ml of bupivacaine 0.5% (a total of 30 ml solution). Sensory block was evaluated with a pinprick test and motor block was evaluated via the Bromage scale by a blinded observer. Results: Block performing time was significantly shorter in the USG group than in the ENSG group (P<0.001). The sensory and motor block onset times were significantly shorter and the additional analgesic requirements were significantly lower in the USG group than in the ENSG group (P<0.001). Conclusion: USG is better than ENSG in axillary brachial plexus block in terms of block performing time, block quality and patient satisfaction.
Symposium on AI, Games and Virtual Reality

Agent design is an intricate process requiring skills from different disciplines. Thus experts in one domain are not necessarily experts in the others. Supporting the design of agents is important and needs to address varying skill and expertise as well as varying handling the design of complex agents. In this paper, a new agent design toolkit – POSH -SHARP– for intelligent virtual agents (IVAs) and cognitive embodied agents is presented. It was designed to address the need for a robust agent development framework in highly restrictive environments such as the web or smartphones while being useful to both novice and expert users. It includes advanced functionality such as debug support, explicit design rules using a related design methodology and a simple set-up and distribution mechanism to reduce the authoring burden for large iteratively developed agents. The new framework was implemented in C# and contains sample code for different game environments to offer novice users a starting point.