Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimizing the Dosing Regimens of Daptomycin Based on the Susceptible Dose-Dependent Breakpoint against Vancomycin-Resistant Enterococci Infection

Daptomycin, a lipopeptide antibiotic, is one of the therapeutic options used for the treatment of vancomycin-resistant enterococci (VRE). Recently, the Clinical and Laboratory Standards Institute (CLSI) M100 30th edition has removed the susceptibility (S) breakpoint for Enterococcus faecium and replaced it with a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL, with a suggested dosage of 8–12 mg/kg/day. Herein, we aimed to determine the minimum inhibitory concentration (MIC) values of daptomycin against clinical VRE isolates and to study the appropriate daptomycin dosing regimens among critically ill patients based on the new susceptibility CLSI breakpoint. The MIC determination of daptomycin was performed using E-test strips among clinical VRE strains isolated from patients at the Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the ratio of the free area under the curve to MIC (fAUC0–24/MIC) > 27.4 and fAUC0–24/MIC > 20 for survival and microbiological response, respectively, at the first day and steady state. Further, we determined that the simulated daptomycin dosing regimen met the minimum concentration (Cmin) requirements for safety of being below 24.3 mg/L. All of the 48 VRE isolates were E. faecium strains, and the percentiles at the 50th and 90th MIC of daptomycin were 1 and 1.5 μg/mL, respectively. At MIC ≤ 2 μg/mL, a daptomycin dosage of 12 mg/kg/day achieved the PTA target of survival and microbiological response at the first 24 h time point and steady state. For a MIC of 4 μg/mL, none of the dosage regimens achieved the PTA target. For CFR, a dosage of 8–12 mg/kg/day could achieve the 90% CFR target at the first day and steady state. All dosing regimens had a low probability of Cmin being greater than 24.3 mg/L. In conclusion, the MIC of VRE against daptomycin is quite low, and loading and maintenance doses with 8 mg/kg/day were determined to be optimal and safe.
Chikungunya Epidemic Mortality in India: Lessons from 17th Century Bills of Mortality Still Relevant

Chikungunya is a virus spread by the bite of the Aedes mosquito, which recently reemerged as a massive epidemic in the Indian Ocean islands and India. Chikungunya is generally considered self-limiting and has been reported as non-fatal but, since March 2005, one-third of the 770,000 people in the Indian Ocean Island of Reunion (a French territory) have been affected by Chikungunya with 237 deaths. India reported 1.3 million cases of Chikungunya however the Government of India has not reported any deaths. However there is evidence that deaths due to Chikungunya did occur. The lack of official reports of deaths is mainly due to the poor recording of ‘Causes of Death’ in India. The London Bills of Mortality from the 17th provides a very good example of the importance of proper reporting of deaths especially during an epidemic period. This paper reflects on the London bills of mortality and modern day lessons to be drawn from it as well as the reasons behind the apparent lack of death reporting in 2006’s Chikungunya epidemic.
Lysine acetyltransferase 8 is involved in cerebral development and syndromic intellectual disability.

Epigenetic integrity is critical for many eukaryotic cellular processes. An important question is how different epigenetic regulators control development and impact disease. Lysine acetyltransferase 8 (KAT8) is critical for acetylation of histone H4 at lysine 16 (H4K16), an evolutionarily conserved epigenetic mark. It is unclear what roles KAT8 plays in cerebral development and human disease. Here, we report that cerebrum-specific knockout mice displayed cerebral hypoplasia in the neocortex and hippocampus, along with improper neural stem and progenitor cell (NSPC) development. Mutant cerebrocortical neuroepithelia exhibited faulty proliferation, aberrant neurogenesis, massive apoptosis and scant H4K16 propionylation. Mutant NSPCs formed poor neurospheres, and pharmacological KAT8 inhibition abolished neurosphere formation. Moreover, we describe KAT8 variants in nine patients with intellectual disability, seizures, autism, dysmorphisms and other anomalies. The variants altered chromobarrel and catalytic domains of KAT8, thereby impairing nucleosomal H4K16 acetylation. Valproate was effective for treating epilepsy in at least two of the individuals. This study uncovers a critical role of KAT8 in cerebral and NSPC development, identifies nine individuals with KAT8 variants, and links deficient H4K16 acylation directly to intellectual disability, epilepsy and other developmental anomalies.
A leader-follower model for discrete competitive facility location problem under the partially proportional rule with a threshold

When consumers are faced with the choice of competitive chain facilities that offer exclusive services, current rules do not properly describe the behavior pattern of these consumers. To eliminate the gap between the current rules and this kind of customers behavior pattern, the partially proportional rule with a threshold is proposed in this paper. A leader-follower model for discrete competitive facility location problem is established under the partially proportional rule with a threshold. Combining with the greedy strategy and the 2-opt strategy, a heuristical algorithm (GFA) is designed to solve the follower’s problem. By embedding the algorithm (GFA), an improved ranking-based algorithm (IRGA) is proposed to solve the leader-follower model. Numerical tests show that the algorithm proposed in this paper can solve the leader-follower model for discrete competitive facility location problem effectively. The effects of different parameters on the market share captured by the leader firm and the follower firm are analyzed in detail using a quasi-real example. An interesting finding is that in some cases the leader firm does not have a first-mover advantage.
Real-time feedback by wearables in running: Current approaches, challenges and suggestions for improvements

ABSTRACT Injuries and lack of motivation are common reasons for discontinuation of running. Real-time feedback from wearables can reduce discontinuation by reducing injury risk and improving performance and motivation. There are however several limitations and challenges with current real-time feedback approaches. We discuss these limitations and challenges and provide a framework to optimise real-time feedback for reducing injury risk and improving performance and motivation. We first discuss the reasons why individuals run and propose that feedback targeted to these reasons can improve motivation and compliance. Secondly, we review the association of running technique and running workload with injuries and performance and we elaborate how real-time feedback on running technique and workload can be applied to reduce injury risk and improve performance and motivation. We also review different feedback modalities and motor learning feedback strategies and their application to real-time feedback. Briefly, the most effective feedback modality and frequency differ between variables and individuals, but a combination of modalities and mixture of real-time and delayed feedback is most effective. Moreover, feedback promoting perceived competence, autonomy and an external focus can improve motivation, learning and performance. Although the focus is on wearables, the challenges and practical applications are also relevant for laboratory-based gait retraining.
Development of Multi-Layer Lateral-Mode Ultrasound Needle Transducer for Brain Stimulation in Mice

Ultrasound, a non-invasive stimulation method, has proved effective in neurostimulation. Previous studies have demonstrated that low-frequency ultrasound (less than 1 MHz) is preferable owing to better penetrability through tissue and skull. However, the large size of low-frequency transducers, which are used in ultrasound neurostimulation studies, makes it difficult to perform multiple-target neurostimulation, especially in small animals such as mice. In this paper, a proposed low-frequency ultrasound needle transducer based on the multi-layer lateral-mode coupling method with a miniature aperture of 0.6 mm × 0.6 mm and a thickness of 1.65 mm was designed and fabricated. The measured electrical impedance of the fabricated 8-layer lateral-mode PZT-5H ceramic was 50.76 Ω at a resonant frequency of 866 kHz. The −6 dB bandwidth of 8-layer lateral-mode transducer was 29% at a center frequency of 876 kHz. The maximum ultrasound peak pressure amplitude at 820 kHz reached approximately 300 kPa, 4–5 times higher than that of the single-layer thickness-mode transducer with 200 V input voltage. The ultrasound beam showed no attenuation and low shift through mouse skull. To verify the feasibility of using the needle transducer to perform multiple-target nerve stimulation in mice brains, we constructed an ultrasound stimulus system to simultaneously stimulate two areas (M2 and V1) of the mouse brain in vivo and detected the c-Fos expression by immunofluorescence to evaluate the effect of stimulation. The results showed that a high ultrasound peak pressure amplitude with this transducer configuration is useful for ultrasound neurostimulation and multiple-target stimulation in mice.
Seasonal Local Models for Glucose Prediction in Type 1 Diabetes

Linear empirical dynamic models have been widely used for blood glucose prediction and risks prevention in people with type 1 diabetes. More accurate blood glucose prediction models with longer prediction horizon (PH) are desirable to enable warnings to patients about imminent blood glucose changes with enough time to take corrective actions. In this study, a blood glucose prediction method is developed by integrating the predictions of a set of seasonal local models (each of them corresponding to different glucose profiles observed along historical data). In the modeling step, the number of sets and their corresponding glucose profiles characteristics are obtained by clustering techniques (Fuzzy C-Means). Then, Box-Jenkins methodology is used to identify a seasonal model for each set. Finally, blood glucose predictions of local models are integrated using different techniques. The proposed method is tested by using 18 60-h closed-loop experiments (including different exercise types and artificial pancreas strategies) and achieving mean absolute percentage error (MAPE) of 2.94%, 3.89%, 5.41%, 6.29% and 8.66% for 15-, 30-, 45-, 60-, and 90-min PHs, respectively.
IMPROVED EFFICACY OF GLICLAZIDE WITH POLYHERBAL FORMULATION ON PHARMACODYNAMIC AND PHARMACOKINETIC ACTIVITY IN NORMAL RABBITS

The present study was carried out to evaluate the polyherbal formulation (PHF) on pharmacodynamic and pharmacokinetics of gliclazide in normal rabbits. A few aqueous extracts of Vinca rosea, Gymnema sylvestre, Tinospora cordifolia, and Emblica officinalis were selected and tested for hypoglycemic and anti hyperglycemic activity on normal and alloxan induced diabetic rats. The optimal doses of the above selected aqueous extracts of Vinca rosea, Gymnema sylvestre, Tinospora cordifolia, and Emblica officinalis were found to be 100, 100, 200 and 300 mg/kg bd.wt. so a polyherbal formulation (PHF) was prepared in the ratio of 1:1:2:3 respectively. In rats the polyherbal formulation was evaluated at three doses 75, 150 and 300 mg/kg bd.wt. and the dose 150 mg/kg that produced an optimal reduction in blood glucose reduction was selected. The same dose is converted to rabbits and a dose of 117 mg/ 1.5 kg bd.wt was selected for the present study. Blood samples were collected by puncturing the marginal veins of rabbits at desired intervals of time and analyzed for blood glucose by GOD-POD method. Gliclazide a second generation sulfonyl urea was selected for the interaction study with that of polyherbal formulation. The human dose of gliclazide is 80 mg/kg bd.wt. Dose response relationship of gliclazide was established with 2.8, 5.6 and 11.2 mg/1.5 kg bd.wt and the dose of 5.6 mg/1.5 kg.bd.wt that produced optimal
Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients

The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt–Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked immunosorbent assay in a cohort of rare genetic prion disease cases, such as genetic CJD (gCJD) cases, exhibiting the E200K, V210I, P102L (Gerstmann–Sträussler–Scheinker syndrome (GSS)), or D178N (fatal familial insomnia (FFI)) mutations in the PRNP. Interestingly, we observed enhanced levels of CSF-MDH1 in all genetic prion disease patients compared to neurological controls (without neurodegeneration). While E200K and V210I carriers showed highest levels of MDH1 with diagnostic discrimination from controls of 0.87 and 0.85 area under the curve (AUC), FFI and GSS patients exhibited only moderately higher CSF-MDH1 levels than controls. An impact of the PRNP codon 129 methionine/valine (MV) genotype on the amount of MDH1 could be excluded. A correlation study of MDH1 levels with other neurodegenerative marker proteins revealed a significant positive correlation between CSF-MDH1 concentration with total tau (tau) but not with 14-3-3 in E200K, as well as in V210I patients. In conclusion, our study indicated the potential use of MDH1 as marker for gCJD patients which may complement the current panel of diagnostic biomarkers.
Hyperkalemia: pathophysiology, risk factors and consequences

Abstract There have been significant recent advances in our understanding of the mechanisms that maintain potassium homoeostasis and the clinical consequences of hyperkalemia. In this article we discuss these advances within a concise review of the pathophysiology, risk factors and consequences of hyperkalemia. We highlight aspects that are of particular relevance for clinical practice. Hyperkalemia occurs when renal potassium excretion is limited by reductions in glomerular filtration rate, tubular flow, distal sodium delivery or the expression of aldosterone-sensitive ion transporters in the distal nephron. Accordingly, the major risk factors for hyperkalemia are renal failure, diabetes mellitus, adrenal disease and the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or potassium-sparing diuretics. Hyperkalemia is associated with an increased risk of death, and this is only in part explicable by hyperkalemia-induced cardiac arrhythmia. In addition to its well-established effects on cardiac excitability, hyperkalemia could also contribute to peripheral neuropathy and cause renal tubular acidosis. Hyperkalemia—or the fear of hyperkalemia—contributes to the underprescription of potentially beneficial medications, particularly in heart failure. The newer potassium binders could play a role in attempts to minimize reduced prescribing of renin–angiotensin inhibitors and mineraolocorticoid antagonists in this context.
Good News for Nuclear Transgene Expression in Chlamydomonas

Chlamydomonas reinhardtii is a well-established model system for basic research questions ranging from photosynthesis and organelle biogenesis, to the biology of cilia and basal bodies, to channelrhodopsins and photoreceptors. More recently, Chlamydomonas has also been recognized as a suitable host for the production of high-value chemicals and high-value recombinant proteins. However, basic and applied research have suffered from the inefficient expression of nuclear transgenes. The combined efforts of the Chlamydomonas community over the past decades have provided insights into the mechanisms underlying this phenomenon and have resulted in mutant strains defective in some silencing mechanisms. Moreover, many insights have been gained into the parameters that affect nuclear transgene expression, like promoters, introns, codon usage, or terminators. Here I critically review these insights and try to integrate them into design suggestions for the construction of nuclear transgenes that are to be expressed at high levels.
Data Uploading Strategy for Underwater Wireless Sensor Networks

Underwater wireless sensor networks (UWSNs) have become a popular research topic due to the challenges of underwater communication. The existing mechanisms for collecting data from UWSNs focus on reducing the data redundancy and communication energy consumption, while ignoring the problem of energy-saving transmission after compression. In order to improve the efficiency of data collection, we propose a data uploading decision-making strategy based on the high similarity of the collected data and the energy consumption of the high similarity data compression. This decision-making strategy efficiently optimizes the energy consumption of the networks. By analyzing the data similarity, the quality of network communication, and uploading energy consumption, the decision-making strategy provides an energy-efficient data upload strategy for underwater nodes, which reduces the energy consumption in various network settings. The simulation results show that compared with several existing data compression and uploading methods, the proposed data upload methods has better energy saving effect in different network scenarios.
Prevalence of Urinary Schistosomiasis Infection among Primary School Pupils in Ezza-North Local Government Area of Ebonyi State

Prevalence of urinary schistosomiasis in apparently healthy school pupils in EzzaNorth Local Government Area was studied. Three hundred and twenty five (325) samples of urine were analysed.Ordinary centrifugal sedimentation technique was used and the deposits were examined microscopically. Out of the 325 urine samples analysed, 57 were found to be positive for Schistosoma haematobium giving a prevalence of 17.5%. Analysis of the result from the schools studied showed that 30 out of 120 from Ogharugo primary school had S. haematobium in their urine while 18 out of 100 from Okposi Primary school and 9 out of 105 from Umuezeoka primary school were positive for S. haematobium. This gives a prevalence of 25.0%, 18.0% and 8.6% respectively. From the result, it was found out that 24.3% of the males had S. haematobium as against 12.4% of the females. The pupils below the ages of 10 years had a prevalence of 7.7% while those of the 10-16 years had that of 24.1%. K e y w o r d s
Multiparametric classification of sub‐acute ischemic stroke recovery with ultrafast diffusion, 23Na, and MPIO‐labeled stem cell MRI at 21.1 T

MRI leverages multiple modes of contrast to characterize stroke. High‐magnetic‐field systems enhance the performance of these MRI measurements. Previously, we have demonstrated that individually sodium and stem cell tracking metrics are enhanced at ultrahigh field in a rat model of stroke, and we have developed robust single‐scan diffusion‐weighted imaging approaches that utilize spatiotemporal encoding (SPEN) of the apparent diffusion coefficient (ADC) for these challenging field strengths. Here, we performed a multiparametric study of middle cerebral artery occlusion (MCAO) biomarker evolution focusing on comparison of these MRI biomarkers for stroke assessment during sub‐acute recovery in rat MCAO models at 21.1 T. T2‐weighted MRI was used as the benchmark for identification of the ischemic lesion over the course of the study. The number of MPIO‐induced voids measured by gradient‐recalled echo, the SPEN measurement of ADC, and 23Na MRI values were determined in the ischemic area and contralateral hemisphere, and relative performances for stroke classification were compared by receiver operator characteristic analysis. These measurements were associated with unique time‐dependent trajectories during stroke recovery that changed the sensitivity and specificity for stroke monitoring during its evolution. Advantages and limitations of these contrasts, and the use of ultrahigh field for multiparametric stroke assessment, are discussed.
Molecular Cavity Topological Representation for Pattern Analysis: A NLP Analogy-Based Word2Vec Method

Cavity analysis in molecular dynamics is important for understanding molecular function. However, analyzing the dynamic pattern of molecular cavities remains a difficult task. In this paper, we propose a novel method to topologically represent molecular cavities by vectorization. First, a characterization of cavities is established through Word2Vec model, based on an analogy between the cavities and natural language processing (NLP) terms. Then, we use some techniques such as dimension reduction and clustering to conduct an exploratory analysis of the vectorized molecular cavity. On a real data set, we demonstrate that our approach is applicable to maintain the topological characteristics of the cavity and can find the change patterns from a large number of cavities.
A CLINICAL STUDY ON EFFECT OF HEALTHY LIFESTYLE IN THE MANAGEMENT OF MIGRAINE

Migraine is a syndrome of episodic and recurrent headache, usually accompanied with nausea, vomiting, photophobia and phonophobia. It is a highly prevalent headache disorder over the past decade having considerable impact on the individual and society. Prevalence of Migraine significantly increases due to various triggering factors and most of the triggers are related with variety of dietary items, daily routine, environmental factors, alcohol, stress etc. In Ayurveda a similar type of disease is described as Ardhavabhedaka, in which excruciating or piercing type of headache felt in one half of the head. It occurs suddenly after a fortnight or ten days, due to abnormality in Vata, Pittta, and Kapha dosha. Pathya Ahara and Vihara are considered as the premier causes to maintain homeostasis of all doshas and prevention of diseases. Although drug therapy provides instant relief but don’t cure the disease permanently and accompanied with many side effects and contraindications. Therefore, the alternative nonpharmacological approaches for prevention and management of Migraine have to be explored. A clinical study was conducted to assess the role of Healthy Lifestyle (including diet and behaviour) on the symptoms of Migraine. Total 20 patients of Migraine were registered and specific dietary articles and behaviour were indicated and contraindicated to them. 17 patients completed all the three follow-ups, each of one month intervals. Frequency
Extending XCS with Representation in First-Order Logic

Since the introduction of Xcs there have been many derivative systems supporting alternative rule languages such as languages over reals, fuzzy logic, S-expressions and even neural networks. This paper describes Foxcs, a derivative of Xcs for learning rules in first-order logic. The Foxcs system is aimed at solving tasks in model-free, relational environments, and is generally applicable to Inductive Logic Programming (ILP) and Relational Reinforcement Learning (RRL). The system was evaluated on several benchmarking ILP tasks where it was found to perform at a level comparable to a number of well-known ILP algorithms with regard to its predictive accuracy. This finding validates the approach of using evolutionary heuristics for discovering rules in first-order logic under the reinforcement learning paradigm, and establishes the system as a promising alternative for RRL.