Miracle-dz/UniFAR-FTUs huggingface dataset:
Relevance of the Weber effect in contemporary pharmacovigilance of oncology drugs

Background Numerous reporting biases have been known to affect spontaneous reporting databases. The Weber effect, which constitutes a peak in adverse event (AE) reporting of a drug at the end of second year after regulatory approval followed by a continuous decline thereafter, has been considered an important bias for a long time. The existence of this bias in AE reporting of oncology drugs remains an underevaluated area, prompting a targeted examination. Methods The US Food and Drug Administration (USFDA) Adverse Event Reporting System (FAERS) was studied for AE reporting patterns of 5 years of 15 new molecular entities (NMEs) and biologics used in oncology. This 5-year period started from the USFDA date of approval for the NMEs and biologics. The number of AEs reported for each of the drugs was plotted against time (years). The AE reporting patterns were specifically examined for the existence of the Weber effect. In addition, AE reporting rate patterns of 5 years of seven NMEs and biologics used in oncology were examined. Results A total of 50,630 AE reports were logged in to the FAERS for all 15 drugs examined for AE reporting patterns. We observed five distinct AE reporting patterns for 15 drugs; however, none of the AE patterns were identical to the Weber effect. We did not observe a consistent AE reporting rate pattern for the seven drugs examined for AE reporting rates. With the exception of one drug (cetuximab), none of the drugs exhibited a second-year peak in AE reporting rates. This peak was not followed by continuous decline in AE reporting rate thereafter. Conclusion This study does not support the existence of the Weber effect in AE reporting of oncology drugs. The contemporary AE reporting of oncology drugs does not exhibit a consistent pattern.
Branched-Chain Amino Acids and Arginine Improve Performance in Two Consecutive Days of Simulated Handball Games in Male and Female Athletes: A Randomized Trial

The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days. Methods: Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34±0.60%, PB trial: -0.21±0.69%; second half: AA trial: -1.68±0.58%, PB trial: 0.49±0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2±0.3) than the PB trial (15.1±0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.
Rice WRKY45 Plays a Crucial Role in Benzothiadiazole-Inducible Blast Resistance[W][OA]

Benzothiadiazole (BTH) is a so-called plant activator and protects plants from diseases by activating the salicylic acid (SA) signaling pathway. By microarray screening, we identified BTH- and SA-inducible WRKY transcription factor (TF) genes that were upregulated within 3 h after BTH treatment. Overexpression of one of them, WRKY45, in rice (Oryza sativa) markedly enhanced resistance to rice blast fungus. RNA interference–mediated knockdown of WRKY45 compromised BTH-inducible resistance to blast disease, indicating that it is essential for BTH-induced defense responses. In a transient expression system, WRKY45 activated reporter gene transcription through W-boxes. Epistasis analysis suggested that WRKY45 acts in the SA signaling pathway independently of NH1, a rice ortholog of Arabidopsis thaliana NPR1, which distinguishes WRKY45 from known Arabidopsis WRKY TFs. Two defense-related genes, encoding a glutathione S-transferase and a cytochrome P450, were found to be regulated downstream of WRKY45 but were not regulated by NH1, consistent with the apparent independence of the WRKY45- and NH1-dependent pathways. Defense gene expression in WRKY45-overexpressed rice plants varied with growth conditions, suggesting that some environmental factor(s) acts downstream of WRKY45 transcription. We propose a role for WRKY45 in BTH-induced and SA-mediated defense signaling in rice and its potential utility in improving disease resistance of rice, an importance food resource worldwide.
Visitors of Parque Florestal Quedas do Rio Bonito, Lavras (Mg), Brazil: a management planning based on profile, perceptions, needs and motivations

The research was carried out in the Parque Florestal Quedas do Rio Bonito, located in Lavras city (Minas Gerais – Brazil) and participatory research methods were used in an integrated and iterative way. Results of the specific visitors study has shown that most of people visit the area with a special interest on leisure opportunities. Enjoyment of natural environment, peace and quiet are also important motivations. In a variety of activities, the visitors appreciate relaxing and enjoying the nature, swimming in the waterfall and walking on the trails. Most of visitors exhibited a high level of interest in conservation. In conclusion, this study represents one of the first efforts for providing the local foundation for a comprehensive framework for outdoor recreation management from the perspective of visitors. More generally, the visitor approach taken in this study contributes to a greater understanding of the visitor experience for tourism management in the natural environments.
Life-Cycle Patterns in the Design and Adoption of Default Funds in DC Pension Plans

We argue that we should see a negative relationship between the share of risky assets in the default fund of a defined contribution (DC) pension plan and the average plan member age if trustees design the default fund in line with predictions from the life-cycle portfolio choice theory. Adoption of the default fund should be low in DC plans with high member age dispersion if default funds are indeed designed for the average plan member and members become aware of this. From analyzing a panel data set of Australian DC pension plans, we obtain results that are consistent with both hypotheses.
Long-Term Potentiation in Hippocampus Involves Sequential Activation of Soluble Guanylate Cyclase, cGMP-Dependent Protein Kinase, and cGMP-Degrading Phosphodiesterase

Previous studies indicate that cGMP is involved in long-term potentiation (LTP). However, the effects of application of tetanus to induce LTP on cGMP content and the mechanisms by which cGMP may modulate LTP have not been reported. The aim of this work was to study the time course of the changes in cGMP content and of the activity of soluble guanylate cyclase (sGC) (the enzyme that synthesizes cGMP) during LTP. Moreover, we also studied how the changes in cGMP affect cGMP-dependent protein kinase (PKG) and cGMP-degrading phosphodiesterase and the possible role of these changes in LTP. Application of tetanus induced a rise in cGMP, reaching a maximum 10 sec after tetanus. cGMP content decreased below basal levels 5 min after tetanus and remained decreased after 60 min. Activity of sGC increased 5 min after tetanus and returned to basal at 60 min. Tetanus increased the activity of cGMP-degrading phosphodiesterase at 5 and 60 min. GMP, the product of degradation, was increased at 5 and 60 min. Activation of phosphodiesterase and a decrease in cGMP were prevented by inhibiting PKG with Rp-8-bromoguanosine-cGMPS (Rp-8-Br-cGMPS). Inhibition of sGC [with ODQ (oxadiazolo quinoxalin-1-one) or NS 2028 (4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one)], of PKG (with Rp-8-Br-cGMPS), or of cGMP-degrading phosphodiesterase [with zaprinast or MBAM (4-{[3′,4′-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline) ] impairs LTP. The results indicate that induction of LTP involves transient activation of sGC and an increase in cGMP, followed by activation of cGMP-dependent protein kinase, which, in turn, activates cGMP-degrading phosphodiesterase, resulting in long-lasting reduction of cGMP content.
Mendelian randomization analysis reveals a causal effect of Streptococcus salivarius on diabetic retinopathy through regulating host fasting glucose

Abstract Diabetic retinopathy (DR) is one of leading causes of vision loss in adults with increasing prevalence worldwide. Increasing evidence has emphasized the importance of gut microbiome in the aetiology and development of DR. However, the causal relationship between gut microbes and DR remains largely unknown. To investigate the causal associations of DR with gut microbes and DR risk factors, we employed two‐sample Mendelian Randomization (MR) analyses to estimate the causal effects of 207 gut microbes on DR outcomes. Inputs for MR included Genome‐wide Association Study (GWAS) summary statistics of 207 taxa of gut microbes (the Dutch Microbiome Project) and 21 risk factors for DR. The GWAS summary statistics data of DR was from the FinnGen Research Project. Data analysis was performed in May 2023. We identified eight bacterial taxa that exhibited significant causal associations with DR (FDR < 0.05). Among them, genus Collinsella and species Collinsella aerofaciens were associated with increased risk of DR, while the species Bacteroides faecis, Burkholderiales bacterium_1_1_47, Ruminococcus torques, Streptococcus salivarius, genus Burkholderiales_noname and family Burkholderiales_noname showed protective effects against DR. Notably, we found that the causal effect of species Streptococcus salivarius on DR was mediated through the level of host fasting glucose, a well‐established risk factor for DR. Our results reveal that specific gut microbes may be causally linked to DR via mediating host metabolic risk factors, highlighting potential novel therapeutic or preventive targets for DR.
An analysis of 342 patients with refractory gastroesophageal reflux disease symptoms using questionnaires, high-resolution manometry, and impedance-pH monitoring

Abstract Symptoms of refractory gastroesophageal reflux disease (GERD) are commonly encountered in clinical practice. The aim of this study was to analyze the data obtained from questionnaires, high-resolution manometry (HRM), and ambulatory impedance-pH monitoring in patients with persisting GERD symptoms and to explore the possible underlying causes for this clinical presentation. After completing the questionnaires, the selected patients underwent endoscopy, HRM, and ambulatory impedance-pH monitoring. Based on the results of these investigations, we divided the patients into 4 groups: reflux esophagitis (RE), hypersensitive esophagus (HE), functional heartburn (FH), and nonerosive gastroesophageal reflux disease (NERD). The data from 342 patients were analyzed. One hundred twenty-nine (37.72%) patients experienced refractory GERD symptoms related to acid reflux. The scores on some scales in the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire differed significantly among groups (all P < 0.05). Liquid reflux occurred more frequently in patients with GERD (RE and NERD), while gas reflux was more common in non-GERD patients (FH and HE; all P < 0.05). The RE and NERD groups showed more percent bolus exposure time (BET) when upright (all P < 0.05). Acid exposure time (AET) in the RE and NERD groups was longer than that in the HE and FH groups (all P < 0.05). Fewer than half of the patient symptoms were related to acid reflux. The GSRS questionnaire may be an optimal indicator for patients with refractory GERD symptoms. BET and AET are useful indices to distinguish GERD from other diseases. Gas reflux is probably related to persisting symptoms in FH and HE patients.
Random Coefficient Models for Time-Series—Cross-Section Data: Monte Carlo Experiments

This article considers random coefficient models (RCMs) for time-series—cross-section data. These models allow for unit to unit variation in the model parameters. The heart of the article compares the finite sample properties of the fully pooled estimator, the unit by unit (unpooled) estimator, and the (maximum likelihood) RCM estimator. The maximum likelihood estimator RCM performs well, even where the data were generated so that the RCM would be problematic. In an appendix, we show that the most common feasible generalized least squares estimator of the RCM models is always inferior to the maximum likelihood estimator, and in smaller samples dramatically so.
Robust Decoding of Upper-Limb Movement Direction Under Cognitive Distraction With Invariant Patterns in Embedding Manifold

Motor brain-computer interfaces (BCIs) have gained growing research interest in motor rehabilitation, restoration, and prostheses control. Decoding upper-limb movement direction with noninvasive BCIs has been extensively investigated. However, few of them address the intervention of cognitive distraction that impairs decoding performance in practice. In this study, we propose a novel decoding model with invariant patterns in embedding manifold on a mixed dataset pooled from electroencephalograph (EEG) signals under different attentional states. We reconstruct an embedding low-dimensional manifold that intrinsically characterizes movements of the upper limb and transfer patterns of neural activities decomposed from brain functional connectivity (FC) to the manifold subspace to further preserve movement-related information. Experimental results showed that the proposed decoding model had higher robustness on the mixed dataset of attentive and distracted states compared to the baseline method. Our research provides insights into modeling a uniform underlying mechanism of movement-related EEG signals and can help enhance the practicability of BCI systems under real-world situations.
Spatiotemporal variation of notified Barmah Forest virus infections in Queensland, Australia, 1993 – 2001

The spatiotemporal variations of Barmah Forest virus (BFv) infections were assessed in Queensland, Australia, between 1993 and 2001 utilizing a Geographic Information System. The notified BFv cases came from 441 localities between 1993 and 1995, 512 between 1996 and 1998, and 546 between 1999 and 2001. A statistically significant increase was observed in the number of localities from which the cases were notified by 16.1% for the period of 1996 – 1998 and 23.8% for 1999 – 2001, compared with that for 1993 – 1995 (χ2 (df = 2) = 11.5; p < 0.01). These results indicate that there has been an expanded geographic distribution of the notified BFv infections in Queensland over the last decade. Socio-ecological changes may be causal factors in this expansion.
Assessment of Developmental Toxicants using Human Embryonic Stem Cells

Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.
An in vitro microbial-based model for studying caries-preventive agents

Objective. The aim of the study was to develop an in vitro microbial-based caries model to test potentially caries-preventive agents. Material and methods. In this model, cariogenic Streptococcus mutans biofilms are grown on tooth samples within a reaction chamber hermetically surrounded by a bacteria-tight glove box allowing the manipulation of specimens during operation. The specimens were mounted in two rows on the inner and outer rims of a specimen turntable passing several inlet pipes transporting all necessary media. Using 64 lower incisors in 4 experiments, a 10 ppm NaF solution and an experimental potentially caries-preventive glycan solution were tested compared to a water control. The mean lesion depth was determined by confocal laser scanning microscopy. Results. The depths of the caries-like lesions showed no statistically significant difference irrespective of whether the specimens were mounted on the inner or outer rim of the specimen turntable. As expected, the NaF solution inhibited the development of caries-like lesions almost completely. The experimental glycan solution revealed a statistically significantly lower demineralization depth compared to the control and a significantly higher depth compared to the NaF group. The system could be operated over a period of more than 9 weeks without unintentional contamination and the manipulation of the tooth specimens could be accomplished. Conclusions. In conclusion, our in vitro system is suitable for testing potential caries-preventive agents in a reproducible way by using whole tooth samples and offers full access together with the possibility of manipulating the specimens during operation.
Rates of convergence in the source coding theorem, in empirical quantizer design, and in universal lossy source coding

Rates of convergence results are established for vector quantization. Convergence rates are given for an increasing vector dimension and/or an increasing training set size. In particular, the following results are shown for memoryless real valued sources with bounded support at transmission rate R. (1) If a vector quantizer with fixed dimension k is designed to minimize the empirical MSE with respect to m training vectors, then its MSE for the true source converges almost surely to the minimum possible MSE as O(/spl radic/(log m/m)); (2) The MSE of an optimal k-dimensional vector quantizer for the true source converges, as the dimension grows, to the distortion-rate function D(R) as O(/spl radic/(log k/k)); (3) There exists a fixed rate universal lossy source coding scheme whose per letter MSE on n real valued source samples converges almost surely to the distortion-rate function D(R) as O(/spl radic/(log log n/log n)); and (4) Consider a training set of n real valued source samples blocked into vectors of dimension k, and a k-dimensional vector quantizer designed to minimize the empirical MSE with respect to the m=[n/k] training vectors. Then the MSE of this quantizer for the true source converges almost surely to the distortion-rate function D(R) as O(/spl radic/(log log n/log n)), if one chooses k=[1/R(1-/spl epsiv/)(log n)] /spl forall//spl epsiv/ /spl epsiv/(0,1). <<ETX>>
Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish

As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate sleep remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior. Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt-overexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate and maintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.
Evaluating the suitability of maggot meal as a partial substitute of soya bean on the productive traits, digestibility indices and organoleptic properties of broiler meat.

This study was conducted to replace soya bean meal with maggot meal at difference percentages. A total of 120 one-day-old broiler chicks were divided into four groups. Four diets were formulated with maggot meal to replace soya bean meal at the rate of 0%, 10%, 20% and 30% designated as A, B, C and D respectively. Feed and water were offered ad libitum during the study which lasted for 28 days. Feed intake decreased significantly in treated groups while body weight, Feed conversion ratio and dressing percentage increased significantly in group D. Apparent metabolizable energy increased significantly in the group fed 30% maggot meal; however, no significant difference was found in dry matter, crude protein, crude fibre, ether extract, ash and nitrogen free extract between the control and treated groups. The result of sensory evaluation revealed that tenderness and juiciness increased significantly in group C and B respectively. The colour and flavour were most accepted in group B and C. The results indicate that replacement of soya bean meal at the rate of 30% in broiler feed produced most favourable results.
Smoothness Properties of Lie Group Subdivision Schemes

Linear stationary subdivision rules take a sequence of input data and produce ever denser sequences of subdivided data from it. They are employed in multiresolution modeling and have intimate connections with wavelet and more general pyramid transforms. Data which naturally do not live in a vector space, but in a nonlinear geometry like a surface, symmetric space, or a Lie group (e.g., motion capture data), require different handling. One way to deal with Lie group valued data has been proposed by Donoho [talk at the IMI Approximation and Computation Meeting, Charleston, SC, 2001]: It is to employ a logexponential analogue of a linear subdivision rule. While a comprehensive discussion of applications is given by Ur Rahman et al. [Multiscale Model. Simul. , 4 (2005), pp. 1201–1232], this paper analyzes convergence and smoothness of such subdivision processes and shows that the nonlinear schemes essentially have the same properties regarding $C^1$ and $C^2$ smoothness as the linear schemes they are derived from.