Miracle-dz/UniFAR-FTUs huggingface dataset:
Increase in colonic diverticular hemorrhage and confounding factors.

AIM To classify changes over time in causes of lower gastrointestinal bleeding (LGIB) and to identify factors associated with changes in the incidence and characteristics of diverticular hemorrhage (DH). METHODS A total of 1803 patients underwent colonoscopy for overt LGIB at our hospital from 1995 to 2013. Patients were divided into an early group (EG, 1995-2006, n = 828) and a late group (LG, 2007-2013, n = 975), and specific diseases were compared between groups. In addition, antithrombotic drug (ATD) use and nonsteroidal anti-inflammatory drug (NSAID) use were compared between patients with and without DH. RESULTS Older patients (≥ 70 years old) and those with colonic DH were more frequent in LG than in EG (P < 0.01). Patients using ATDs as well as NSAIDs, male sex, obesity (body mass index ≥ 25 kg/m(2)), smoking, alcohol drinking, and arteriosclerotic diseases were more frequent in patients with DH than in those without. CONCLUSION Incidence of colonic DH seems to increase with aging of the population, and factors involved include use of ATDs and NSAIDs, male sex, obesity, smoking, alcohol drinking, and arteriosclerotic disease. These factors are of value in handling DH patients.
Fluoroquinolone Enhances the Mutation Frequency for Meropenem-Selected Carbapenem Resistance in Pseudomonas aeruginosa, but Use of the High-Potency Drug Doripenem Inhibits Mutant Formation

ABSTRACT The mutation frequency for carbapenem resistance in Pseudomonas aeruginosa strains that were selected with carbapenems was enhanced in the presence of subinhibitory concentrations of fluoroquinolones. The mutants showed either a loss of OprD activity or increased mexAB-oprM expression. The highest mutant isolation frequency was obtained by selection with meropenem, while doripenem inhibited mutant growth.
Phylogenomics of Ligand-Gated Ion Channels Predicts Monepantel Effect

The recently launched veterinary anthelmintic drench for sheep (Novartis Animal Health Inc., Switzerland) containing the nematocide monepantel represents a new class of anthelmintics: the amino-acetonitrile derivatives (AADs), much needed in view of widespread resistance to the classical drugs. Recently, it was shown that the ACR-23 protein in Caenorhabditis elegans and a homologous protein, MPTL-1 in Haemonchus contortus, are potential targets for AAD action. Both proteins belong to the DEG-3 subfamily of acetylcholine receptors, which are thought to be nematode-specific, and different from those targeted by the imidazothiazoles (e.g. levamisole). Here we provide further evidence that Cel-ACR-23 and Hco-MPTL-1-like subunits are involved in the monepantel-sensitive phenotype. We performed comparative genomics of ligand-gated ion channel genes from several nematodes and subsequently assessed their sensitivity to anthelmintics. The nematode species in the Caenorhabditis genus, equipped with ACR-23/MPTL-1-like receptor subunits, are sensitive to monepantel (EC50<1.25 µM), whereas the related nematodes Pristionchus pacificus and Strongyloides ratti, which lack an ACR-23/MPTL-1 homolog, are insensitive (EC50>43 µM). Genome sequence information has long been used to identify putative targets for therapeutic intervention. We show how comparative genomics can be applied to predict drug sensitivity when molecular targets of a compound are known or suspected.
The impact of long‐term antihypertensive treatment on wound healing after major non‐cardiac surgery in patients with cardiovascular diseases: A meta‐analysis

Abstract Hypertension is a prevalent condition that poses significant challenges in the perioperative management of patients undergoing major non‐cardiac surgery, particularly concerning wound healing and scar formation. This meta‐analysis assesses the impact of long‐term antihypertensive treatment on postoperative wound healing, examining data from seven studies involving patients who received such treatments compared to untreated controls. Our findings reveal that long‐term antihypertensive therapy is associated with significantly improved wound healing outcomes, as indicated by lower REEDA scores (I 2 = 96%, SMD = −25.71, 95% CI: [−33.71, −17.70], p < 0.01) 1 week post‐surgery and reduced scar formation, demonstrated by lower Manchester Scar Scale scores (I 2 = 93%, SMD = −37.29, 95% CI: [−44.93, −29.64], p < 0.01) 2 months post‐surgery. These results underscore the potential benefits of antihypertensive treatment in enhancing surgical recovery and offer insights into optimising perioperative care for hypertensive patients.
Estimating models of inverse systems

This paper considers the problem of how to estimate a model of the inverse of a system. The use of inverse systems can be found in many applications, such as feedforward control and power amplifier predistortion. The inverse model is here estimated with the purpose of using it in cascade with the system itself, as an inverter. A good inverse model in this setting would be one that, when used in series with the original system, reconstructs the original input. The goal here is to select suitable inputs, experimental conditions and loss functions to obtain a good input estimate. Both linear and nonlinear systems will be discussed. For nonlinear systems, one way to obtain a linearizing prefilter is by Hirschorn's algorithm. It is here shown how to extend this to the postdistortion case, and some formulations of how the pre- or postinverter could be estimated are also presented.
Monitoring Plastic-Mulched Farmland by Landsat-8 OLI Imagery Using Spectral and Textural Features

In recent decades, plastic-mulched farmland has expanded rapidly in China as well as in the rest of the world because it results in marked increases of crop production. However, plastic-mulched farmland significantly influences the environment and has so far been inadequately investigated. Accurately monitoring and mapping plastic-mulched farmland is crucial for agricultural production, environmental protection, resource management, and so on. Monitoring plastic-mulched farmland using moderate-resolution remote sensing data is technically challenging because of spatial mixing and spectral confusion with other ground objects. This paper proposed a new scheme that combines spectral and textural features for monitoring the plastic-mulched farmland and evaluates the performance of a Support Vector Machine (SVM) classifier with different kernel functions using Landsat-8 Operational Land Imager (OLI) imagery. The textural features were extracted from multi-bands OLI data using a Grey Level Co-occurrence Matrix (GLCM) algorithm. Then, six combined feature sets were developed for classification. The results indicated that Landsat-8 OLI data are well suitable for monitoring plastic-mulched farmland; the SVM classifier with a linear kernel function is superior both to other kernel functions and to two other widely used supervised classifiers: Maximum Likelihood Classifier (MLC) and Minimum Distance Classifier (MDC). For the SVM classifier with a linear kernel function, the highest overall accuracy was derived from combined spectral and textural features in the 90° direction (94.14%, kappa 0.92), followed by the combined spectral and textural features in the 45° (93.84%, kappa 0.92), 135° (93.73%, kappa 0.92), 0° (93.71%, kappa 0.92) directions, and the spectral features alone (93.57%, kappa 0.91). Spectral features make a more significant contribution to monitoring the plastic-mulched farmland; adding textural features from medium resolution imagery provide only limited improvement in accuracy.
Dopamine Alters AMPA Receptor Synaptic Expression and Subunit Composition in Dopamine Neurons of the Ventral Tegmental Area Cultured with Prefrontal Cortex Neurons

Excitatory synapses onto dopamine (DA) neurons of the ventral tegmental area (VTA) represent a critical site of psychostimulant-induced synaptic plasticity. This plasticity involves alterations in synaptic strength through AMPA receptor (AMPAR) redistribution. Here, we report an in vitro model for studying regulation of AMPAR trafficking in DA neurons under control conditions and after elevation of DA levels, mimicking cocaine exposure. We used cocultures containing rat VTA neurons and prefrontal cortex (PFC) neurons from enhanced cyan fluorescent protein-expressing mice. In VTA-PFC cocultures, D1 receptor activation (10 min) increased synaptic and nonsynaptic glutamate receptor subunit 1 (GluR1) and GluR2 surface expression on DA neurons. NMDA or AMPA receptor antagonists blocked this effect, and it was not observed in pure VTA cultures, suggesting that DA agonists acted on D1 receptors on PFC neurons, altering their excitatory transmission onto VTA DA neurons and, thus, influencing AMPARs. To mimic the longer elevation in extracellular DA levels produced by systemic cocaine, cocultures were incubated with DA for 1 h. Synaptic GluR1 was increased 24 h later, reminiscent of the increased AMPA/NMDA ratio at excitatory synapses onto VTA DA neurons 24 h after cocaine injection (Ungless et al., 2001). In contrast, GluR2 was unchanged. Analysis of colocalization of surface GluR1–3 labeling suggested that control DA neurons express a substantial number of GluR1/2, GluR2/3, and homomeric GluR1 receptors and that the increase in surface AMPARs 24 h after DA exposure may in part reflect increased GluR1/3-containing receptors. These results help define the cellular basis for plasticity underlying the development of behavioral sensitization.
Peaking for optimal performance: Research limitations and future directions

Abstract A key element of the physical preparation of athletes is the taper period in the weeks immediately preceding competition. Existing research has defined the taper, identified various forms used in contemporary sport, and examined the prescription of training volume, load, intensity, duration, and type (progressive or step). Current limitations include: the lack of studies on team, combative, racquet, and precision (target) sports; the relatively small number of randomized controlled trials; the narrow focus on a single competition (single peak) compared with multiple peaking for weekly, multi-day or multiple events; and limited understanding of the physiological, neuromuscular, and biomechanical basis of the taper. Future research should address these limitations, together with the influence of prior training on optimal tapering strategies, and the interactions between the taper and long-haul travel, heat, and altitude. Practitioners seek information on how to prescribe tapers from season to season during an athlete's career, or a team's progression through a domestic league season, or multi-year Olympic or World Cup cycle. Practical guidelines for planning effective tapers for the Vancouver 2010 and London 2012 Olympics will evolve from both experimental investigations and modelling of successful tapers currently employed in a wide range of sports.
Activation of Histone Deacetylase 2 by Inducible Heat Shock Protein 70 in Cardiac Hypertrophy

Diverse cardiac diseases induce cardiac hypertrophy, which leads to dilatation and heart failure. We previously reported that hypertrophy can be blocked by class I histone deacetylase (HDAC) inhibitor, which prompted us to investigate the regulatory mechanism of class I HDACs. Cardiac hypertrophy was introduced by aortic banding, by infusion of isoproterenol or angiotensin II, or by swimming. Hypertrophic stimuli transiently elevated the activity of histone deacetylase-2 (Hdac2), a class I HDAC. In cardiomyocytes, forced expression of Hdac2 simulated hypertrophy in an Akt-dependent manner, whereas enzymatically inert Hdac2 H141A failed to do so. Hypertrophic stimuli induced the expression of heat shock protein (Hsp)70. The induced Hsp70 physically associated with and activated Hdac2. Hsp70 overexpression produced a hypertrophic phenotype, which was blocked either by siHdac2 or by a dominant negative Hsp70&Dgr;ABD. In Hsp70.1−/− mice, cardiac hypertrophy and Hdac2 activation were significantly blunted. Heat shock either to cardiomyocytes or to mice activated Hdac2 and induced hypertrophy. However, heat shock-induced Hdac2 activation was blunted in the cardiomyocytes isolated from Hsp70.1−/− mice. These results suggest that the induction of Hsp70 in response to diverse hypertrophic stresses and the ensuing activation of HDAC2 trigger cardiac hypertrophy, emphasizing HSP70/HDAC2 as a novel mechanism regulating hypertrophy.
Emerging preclinical pharmacological targets for Parkinson's disease

Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the pathophysiology of PD has offered a range of potential targets for PD. Several emerging targets including AAV-hAADC gene therapy, phosphodiesterase-4, potassium channels, myeloperoxidase, acetylcholinesterase, MAO-B, dopamine, A2A, mGlu5, and 5-HT-1A/1B receptors are in different stages of clinical development. Additionally, alternative interventions such as deep brain stimulation, thalamotomy, transcranial magnetic stimulation, and gamma knife surgery, are also being developed for patients with advanced PD. As much as these therapeutic targets hold potential to delay the onset and reverse the disease, more targets and alternative interventions need to be examined in different stages of PD. In this review, we discuss various emerging preclinical pharmacological targets that may serve as a new promising neuroprotective strategy that could actually help alleviate PD and its symptoms.
Forecasting Fetal Buprenorphine Exposure through Maternal–Fetal Physiologically Based Pharmacokinetic Modeling

Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal–fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal–fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal–fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.
Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings

The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2–4 events was lower for rilpivirine compared with efavirenz. Grade 3–4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs.
Preventing Adolescents' Diabesity: Design, Development, and First Evaluation of “Gustavo in Gnam's Planet”

Abstract Objective: The goal of this study was to design, develop, and evaluate a game for health, “Gustavo in Gnam's Planet” (“Gustavo”), aimed to improve knowledge on healthy foods and to increase consumption of healthy foods. Subjects and Methods: Eighty-three high school students were enrolled in the study. The game was designed and developed by a multidisciplinary team. Behavioral change theories were adopted to guide the design of the health messages. Participants were assessed about food frequency, healthy food knowledge, and the game's interest. Results: Forty-seven subjects (mean age, 14.9±1.0 years; 72.3 percent males) completed the study. At posttest, participants showed significant higher scores (i.e., increased knowledge) in the questionnaire on knowledge of healthy foods (70.0±9.2 versus 71.3±10.0 for pretest and posttest, respectively; P<0.05). Improvements in healthy eating habits were also detected: higher frequency of consumption during a week of white meat (1 [1–2] versus 2 [1–2]; P=0.01), eggs (1 [1–1] versus 1 [1–2]; P=0.01], and legumes (1 [0–1] versus 1 [1–2]; P=0.03) and lower frequency of consumption of sugar-containing packaged snacks (1 [0–1] versus 0 [0–1]; P=0.009). Most of the participants found the game easy to use and clear in its content. Half of the participants found the game interesting. Conclusions: Our study shows that “Gustavo” is a promising tool for health education, in schools or in other environments. Limitations of the study and future directions are discussed.
Severe cartilage damage from a broken absorbable screw head after fixation of an avulsion fracture of the tibial attachment of the posterior cruciate ligament

Introduction: The use of bioabsorbable interference screws has become popular for treatment of avulsion fractures of the posterior cruciate ligament (PCL). Complications are uncommon. We report a case of severe chondral damage caused by the early breakage of an absorbable screw head after fixation of an avulsion fracture of the tibial attachment of the PCL. The patient felt a sudden locking of the knee when getting off a car at 4 months after the PCL surgery. MRI revealed intraarticular migration of the head of the interference screw. During revision surgery, the broken part was removed without incident, and severe cartilage damage was observed. The patient experienced a complete resolution of symptoms at the 6-month follow-up. Conclusion: MRI examination is recommended in case of sudden locking of the knee for patients undergoing PCL fixation with bioabsorbable interference screws. Surgical treatment should be performed immediately when screw breakage was confirmed.
Role of living donor liver transplantation in the treatment of hepatitis C virus infection

Hepatitis C virus (HCV) infection is one of the most common indications for liver transplantation worldwide. Because of the existing organ shortage, adult-to-adult living donor liver transplantation (LDLT) has become an important method of expanding the donor pool to meet the ever-increasing need. However, despite advantages such as the quality of the hepatic graft and the timing of the transplant, the exact role of LDLT in the treatment of HCV is still unclear. In this review, we aim to address some of these issues in an effort to highlight both the advantages and disadvantages, as well as to identify the main challenges, of using LDLT for treating patients with HCV infection.
STUDIES ON THE EFFECT OF CERTAIN MACROMOLECULAR SUBSTANCES ON THE RESPIRATORY ACTIVITY OF THE LEUCOCYTES OF PERIPHERAL BLOOD

The oxygen, uptake of lightly heparinized human blood was found to increase markedly upon the addition of bacterial endotoxins, soluble antigen-antibody complexes, or polystyrene latex particles. The effect apparently reflects a transitory stimulation of respiratory activity of the blood leucocytes. The effect did not occur in the presence of anticoagulant amounts of citrate or ethylenediaminetetraacetate, was inhibited by iodoacetate and fluoride ions, and may be related to the energy-yielding processes involved in histamine release or phagocytosis.