Miracle-dz/UniFAR-FTUs huggingface dataset:
Solidification drug nanosuspensions into nanocrystals by freeze-drying: a case study with ursodeoxycholic acid

Abstract To elucidate the effect of solidification processes on the redispersibility of drug nanocrystals (NC) during freeze-drying, ursodeoxycholic acid (UDCA) nanosuspensions were transformed into UDCA-NC via different solidification process included freezing and lyophilization. The effect of different concentrations of stabilizers and cryoprotectants on redispersibility of UDCA-NC was investigated, respectively. The results showed that the redispersibility of UDCA-NC was RDI−20 °C < RDI−80 °C < RDI−196 °C during freezing, which indicated the redispersibility of UDCA-NC at the conventional temperature was better more than those at moderate and rigorous condition. Compared to the drying strengthen, the employed amount and type of stabilizers more dramatically affected the redispersibility of UDCA-NC during lyophilization. The hydroxypropylmethylcellulose and PVPK30 were effective to protect UDCA-NC from damage during lyophilization, which could homogeneously adsorb into the surface of NC to prevent from agglomerates. The sucrose and glucose achieved excellent performance that protected UDCA-NC from crystal growth during lyophilization, respectively. It was concluded that UDCA-NC was subjected to agglomeration during solidification transformation, and the degree of agglomeration suffered varied with the type and the amounts of stabilizers used, as well as different solidification conditions. The PVPK30-sucrose system was more effective to protect UDCA-NC from the damage during solidification process.
Noninvasive assessment of liver fibrosis

Liver biopsy has long been an important tool for assessing the degree of liver fibrosis. Information on the presence and degree of liver fibrosis is useful before making therapeutic decisions or predicting disease outcomes. The need to stage liver fibrosis, however, should decrease as treatment options become more successful (as has occurred with viral hepatitis). In recent years, noninvasive tests have demonstrated a reasonable ability to identify significant fibrosis, cirrhosis in particular, nor is it surprising that liver disease specialists and patients favor a noninvasive approach. However, only those tests with the highest diagnostic accuracy, cost‐effectiveness, and availability should be implemented. Apart from their diagnostic accuracy, the potential ability of these tests to predict disease outcomes (a more relevant endpoint) should be compared with that of liver biopsy. Indeed, the use of a standardized system to evaluate the utility of biomarkers would facilitate their implementation in clinical practice. (HEPATOLOGY 2011.)
Genetic polymorphism in metabolism and host defense enzymes: Implications for human health risk assessment

Genetic polymorphisms in xenobiotic metabolizing enzymes can have profound influence on enzyme function, with implications for chemical clearance and internal dose. The effects of polymorphisms have been evaluated for certain therapeutic drugs but there has been relatively little investigation with environmental toxicants. Polymorphisms can also affect the function of host defense mechanisms and thus modify the pharmacodynamic response. This review and analysis explores the feasibility of using polymorphism data in human health risk assessment for four enzymes, two involved in conjugation (uridine diphosphoglucuronosyltransferases [UGTs], sulfotransferases [SULTs]), and two involved in detoxification (microsomal epoxide hydrolase [EPHX1], NADPH quinone oxidoreductase I [NQO1]). This set of evaluations complements our previous analyses with oxidative and conjugating enzymes. Of the numerous UGT and SULT enzymes, the greatest likelihood for polymorphism effect on conjugation function are for SULT1A1 (*2 polymorphism), UGT1A1 (*6, *7, *28 polymorphisms), UGT1A7 (*3 polymorphism), UGT2B15 (*2 polymorphism), and UGT2B17 (null polymorphism). The null polymorphism in NQO1 has the potential to impair host defense. These highlighted polymorphisms are of sufficient frequency to be prioritized for consideration in chemical risk assessments. In contrast, SNPs in EPHX1 are not sufficiently influential or defined for inclusion in risk models. The current analysis is an important first step in bringing the highlighted polymorphisms into a physiologically based pharmacokinetic (PBPK) modeling framework.
Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration

In the present studies, we have established that RSV can elicit a more pathogenic environment dependent on improper DC‐associated sensitization. Our initial studies demonstrated that RSV, but not influenza, infection during an allergen exposure into the airway induced a more severe allergen response. The RSV‐induced exacerbation included an increased Th2 cytokine response and pathophysiology as monitored by AHR and mucus overproduction. DCs played a central role in the allergen‐induced responses, as instilling RSV‐infected BMDC into the airway could recapitulate a live virus challenge. With the use of CCR6−/− mice that have a primary defect in the recruitment of mDC subsets, reduced exacerbation of disease was observed when RSV was administered along with allergen. Furthermore, sensitization of mice with RSV‐infected BMDC into the airway produced a more severe immune response to a live virus challenge. Subsequently, using RSV‐infected BMDC from CCR7−/− mice (that do not migrate efficiently to LNs) to sensitize the exacerbated response demonstrated that the response was dependent on DC migration to the LN. Finally, the ability of RSV‐infected DCs to elicit an exacerbated, allergen‐induced pathogenic response could be maintained for as long as 3 weeks, suggesting that RSV‐infected DCs themselves created an altered immune environment that impacts off‐target mucosal responses that could have prolonged effects.
Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimers

ABSTRACT Ultraviolet radiation (UVR) instantaneously generates cyclobutane pyrimidine dimers (CPDs). Paradoxically, we recently observed that UV enables the protective pigment melanin to create CPDs in the dark long after the exposure ends. UV-induced reactive oxygen species (ROS) oxidize melanin to create melanin carbonyls in a high-energy quantum state. These energetic melanin carbonyls transfer their energy to DNA in the dark, creating CPDs in the absence of UVR.
Treating OSA: Current and emerging therapies beyond CPAP

Continuous positive airway pressure (CPAP) is the standard treatment for moderate‐to‐severe obstructive sleep apnoea (OSA). However, adherence to CPAP is limited and non‐CPAP therapies are frequently explored. Oral appliance (OA) therapy is currently widely used for the treatment of snoring, mild, moderate and severe OSA. The most commonly used and studied OA consists of a maxillary and mandibular splint which hold the lower jaw forward during sleep. The efficacy of OA is inferior to CPAP; however, the effectiveness as measured by sleepiness, quality of life, endothelial function and blood pressure is similar likely due to higher acceptance and subjective adherence. Upper airway stimulation augments neural drive by unilaterally stimulating the hypoglossal nerve. The Stimulation Therapy for Apnea Reduction (STAR) study enrolled 126 patients and demonstrated a 68% reduction in OSA severity. A high upfront cost and variable response are the main limitations. Oropharyngeal exercises consist of a set of isometric and isotonic exercises involving the tongue, soft palate and lateral pharyngeal wall. The collective reported trials (n = 120) showed that oropharyngeal exercises can ameliorate OSA and snoring (~30–40%). Nasal EPAP devices consist of disposable one‐way resister valve. A systematic review (n = 345) showed that nasal EPAP reduced OSA severity by 53%. The Winx device consists of a mouthpiece placed inside the oral cavity that is connected by tubing to a console that generates negative pressure. Winx may provide successful therapy for ~30–40% of OSA patients. In conclusion, several non‐CPAP therapies to treat OSA are currently available.
Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice.

BACKGROUND & AIMS We studied the functions of natural killer (NK) cells and the role of the NK cell inhibitory receptor (NKG2A) during hepatitis B virus (HBV) infection in patients and mice. METHODS We analyzed levels of NKG2A on peripheral blood NK cells from 42 patients with active chronic hepatitis B (CHB), 31 patients with inactive CHB, and 35 healthy volunteers (controls). Five patients with CHB treated with antiviral therapy were also included to evaluate changes in NK cells after HBV titers decreased. We examined the effects of blocking antibodies against NKG2A or its ligand Qa-1 (equivalent to HLA-E in humans) in immunocompetent mice that express HBV from a plasmid and are positive for serum hepatitis B surface antigen (a mouse model of HBV infection). RESULTS A higher percentage of NK cells from patients with active CHB were positive for NKG2A (38.47%) than from patients with inactive CHB (19.33%; P < .01) or controls (27.96%; P < .05). The percentage of NKG2A(+) cells correlated with serum viral load (r = 0.5457; P < .001). The percentage of NKG2A(+) cells decreased along with HBV load in patients that received antiviral therapy (P < .05). Blocking NKG2A interaction with HLA-E in peripheral NK cells from patients with active CHB increased their cytotoxicity in vitro. NK cells of HBV carrier mice also had higher percentages of NK cells that expressed NKG2A compared with control mice; NKG2A was likely to be up-regulated by production of interleukin-10 by hepatic regulatory CD4(+)CD25(+) T cells. Blocking Qa-1 in these mice promoted viral clearance in an NK cell-dependent manner. CONCLUSIONS Infection with HBV increases levels of the inhibitory receptor NKG2A on NK cells in mice and humans, and reduces their ability to clear HBV. Reagents designed to block the interaction between NKG2A and HLA-E might be developed to treat CHB infection.
Experience‐ and age‐mediated oviposition behaviour in the yellow fever mosquito Stegomyia aegypti (=Aedes aegypti)

In repeated behaviours such as those of feeding and reproduction, past experiences can inform future behaviour. By altering their behaviour in response to environmental stimuli, insects in highly variable landscapes can tailor their behaviour to their particular environment. In particular, female mosquitoes may benefit from plasticity in their choice of egg‐laying site as these sites are often temporally variable and clustered. The opportunity to adapt egg‐laying behaviour to past experience also exists for mosquito populations as females typically lay eggs multiple times throughout their lives. Whether experience and age affect egg‐laying (or oviposition) behaviour in the mosquito Stegomyia aegypti (=Aedes aegypti) (Diptera: Culicidae) was assessed using a wind tunnel. Initially, gravid mosquitoes were provided with a cup containing either repellent or well water. After ovipositing in these cups, the mosquitoes were blood‐fed and introduced into a wind tunnel. In this wind tunnel, an oviposition cup containing repellent was placed in the immediate vicinity of the gravid mosquitoes. A cup containing well water was placed at the opposite end of the tunnel so that if the females flew across the chamber, they encountered the well water cup, in which they readily laid eggs. Mosquitoes previously exposed to repellent cups became significantly more likely to later lay eggs in repellent cups, suggesting that previous experience with suboptimal oviposition sites informs mosquitoes of the characteristics of nearby oviposition sites. These results provide further evidence that mosquitoes modify behaviour in response to environmental information and are demonstrated in a vector species in which behavioural plasticity may be ecologically and epidemiologically meaningful.
Selegiline is an efficient and potent inducer for bone marrow stromal cell differentiation into neuronal phenotype

Abstract Objective: Bone marrow stromal cells (BMSCs) were documented as a feasible candidate for cell therapy. Several protocols with one or more steps, using different chemicals, were used for inducing BMSCs differentiation into neuronal phenotype. Many of these chemicals were reported to be of mutagenic, teratogenic or carcinogenic properties. The purpose of this work was to evaluate the neuronal inductivity of selegiline to BMSCs. Methods: Selegiline was used to induce BMSCs following pre-induction with β-mercaptoethanol and retinoic acid. The neuronal phenotype was evaluated using antineurofilament 200, neurofilament 68, anti-Map-2 and synapsin I antibodies. In addition, reverse transcription polymerase chain reaction was used for the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neuroligin 1 and post-synaptic density protein 95 (PSD-95). Results: The result of the work showed that the induced BMSCs were immunoreactive for neurofilaments 200 and 68. Moreover, anti-Map-2 and synapsin I antibodies showed a structure morphologically consistent with synapses. Reverse transcription polymerase chain reaction showed that the induced BMSCs could express BDNF, NGF, NT-3, neuroligin 1 and PSD-95. The time course used was 1, 3, 6, 12, 24, 36 and 48 hours, and the percentages of neurofilament 200 immunoreactive cells were analysed using the logistic growth curve. Discussion: The results showed that selegiline was efficient and a potent inducer for BMSCs into neuronal phenotype, which can be used in the cell therapy in neurodegeneration and traumatic nervous tissue injuries.
Messenger RNA in animal cells.

It is difficult to believe that only 2 years ago, the very existence of messenger RNAs in animal cells was doubtful, and no definitive example of an isolated and purified mRNA could be given. Since that time, the mRNAs for globin (from rabbit, man, mouse, duck, and guinea pig), lens crystallin (chick and cow), ovalbumin, myosin, and silk fibroin have been isolated and their identities confirmed, and histone, protamine, and tubulin mRNAs have been putatively identified. It can be stated with a degree of certainty that if a laboratory has access to a tissue making large amounts of a single protein, and an assay for that protein which is both unique and sensitive, it should be possible to isolate and characterize the mRNA for that protein. Messenger RNA was first identified in bacterial systems by its rapid labelling with radioisotopes, a rapid turnover relative to ribosomal RNA and 'DNA-like' base composition (Gros et al, 1961; Jacob and Monod, 1961). Although similar criteria have been applied to mRNA in some mammalian tissues, such as liver, in general mRNA in a differentiating cell need not differ in labelling or base composition from other RNA species. Therefore attempts were made to obtain stimulation of the synthesis of a specific protein in a mixed cell-free system. It is essential that the cell-free protein synthesis system used should not normally be capable of synthesizing the protein, for there are many factors which can stimulate endogenous protein activity apart from mRNA. An unambiguous assay system for the protein is also necessary, to distinguish it from endogenous protein synthesis characteristic of the cell-free system.
Oral Candida albicans carriage in healthy preschool and school children.

PURPOSE The purpose of the present study was to detect Candida albicans carriage in the oral cavity of healthy preschool and school children. The second aim was the determination of correlation between C. albicans occurrence and dental caries in children population. MATERIAL AND METHODS The samples for mycological examinations were collected from the pharynx and supragingival plaque, and carious lesions in 102 children, aged 4-7 years (preschool children) and 104 children and adolescents, aged 12 and 18 (school children). All samples were cultured directly on Sabouraud agar medium. Isolated yeasts were identified based on API 20C AUX (bioMérieux). RESULTS A total of 123 C. albicans strains were isolated, in which 61 (49.6%) derived from supragingival plaque, 48 (39%)--from carious lesions, and 14 (11.4%)--from pharyngeal swabs. C. albicans was isolated from the samples of single material in 61 children (35--school children, 26 --preschool children) while from the rest of 29 children, C. albicans was isolated from two (25x) or three materials (4x). C. albicans was detected in 48/75 (64%) children with dental caries; the rate was statistically significantly higher as compared to the overall number of children with C. albicans carriage (90/206; 43.7%) (p = 0.0026). Similar results was obtained in preschool children (38/61; 62.3% and 47/102; 46.1%, respectively) (p = 0.0449), as in school children (10/14; 71.4% and 43/104; 41.3%, respectively) (p = 0.0336). CONCLUSIONS 1) Candida albicans was observed in the oral cavity of healthy children with high (approximately 40%)--comparable rate in school and preschool children (p > 0.05). 2) C. albicans was isolated with high comparable rate from carious lesions in preschool and school children. The statistically significant differences between the rate of C. albicans in carious lesions in preschool children (62.3%) and school children (71.4%) and the overall number of children with C. albicans carriage in the oral cavity of children in both age groups (p < 0.05) were showed.
User Roles in Document Analysis

In a modern business process, documents are important carriers of information between organisations. Document management solutions are increasingly based on structured document formats, such as XML (Extensible Markup Language). However, deployment of structured documents is a complicated task, which requires systematic analysis of requirements of all groups either producing or using documents. In this paper, we describe a method for modelling user roles in document analysis. The method is used to support analysis of requirements of individual and organisational users of documents as well as analysis of organisational needs related to security and access control.
Morphological Divergence, Reproductive Isolating Mechanism, and Molecular Phylogenetic Relationships Among Indonesia, Malaysia, and Japan Populations of the Fejervarya limnocharis Complex (Anura, Ranidae)

Abstract In order to elucidate the taxonomic status of the Fejervarya limnocharis complex relative to Malaysia and Japan populations, morphological observations and molecular phylogenetic analysis were carried out using three populations from Indonesia (type locality), Malaysia, and Japan. In addition, we conducted histological and spermatogenic observations using hybrids among these populations. Principal component and cluster analyses demonstrated that these populations could be clearly separated from one another. Abnormal testes were found in the hybrids between the Japan and Indonesia populations and between the Japan and Malaysia populations, but testes of the controls and hybrids between the Malaysia and Indonesia populations were quite normal. The mean number of univalents per cell was 5.42, 4.58, and 0.20 in hybrids between the Indonesia and Japan populations, Malaysia and Japan populations, and Indonesia and Malaysia populations, respectively. Sequence divergences in 16S rRNA and Cyt b genes were 0–0.4% (x̄=0.2%) and 0.3–1.5% (x̄=1.0%), respectively, between the Malaysia and Indonesia populations, and 2.4–2.6% (x̄=2.5%) and 11.0–12.0% (x̄=11.5%) between the Japan population and F. limnocharis complex, including the Malaysia and Indonesia populations and F. multistriata from China. This study indicated that the Malaysia population and F. multistriata from China should be designated as a subspecies of topotypic F. limnocharis, and that the Japan population should be regarded as a distinct species.
The Literature Review on Dual Fuel Diesel-Natural Gas Combustion, Emission and Performance

As a result of the latest trends in the automotive industry that have put stringent requirements on the fuel consumption and exhaust gas emission, the engine research has been directed towards optimization of the combustion process and application of the variety of cleaner fuels. In that context the use of natural gas as a partial supplement for the liquid Diesel fuel has attracted a lot of attention. This paper presents the literature review of recent research on dual fuel Diesel-natural gas operation. It presents the benefits and drawbacks of dual fuel Diesel-natural gas operation as well as the means and methods to circumvent these drawbacks. The use of natural gas as a partial supplement for Diesel liquid fuel has been suggested due to its cleaner nature of combustion, its worldwide availability and its potential to reduce both global (CO2) and local (NOx, soot) exhaust gas emissions from conventional Diesel engines. As natural gas is consisted primarily of methane (CH4), it has high H/C ratio thus having the theoretical potential to reduce the CO2 emission by nearly 25% compared to conventional Diesel fuel. What makes dual fuel operation possible is the flammability limit between the two fuels and it exploits the advantages of each one. Diesel fuel pilot is used as a high energy ignition device (Diesel fuel pilot releases 10000 times more energy compared to the energy delivered by spark the in spark-ignition engine) while natural gas is used as a primary fuel in the operation. Several dual fuel combustion strategies have been proposed ; (a) conventional dual fuel combustion that operates with premixed natural gas which is ignited by the Diesel fuel pilot ; (b) direct injected dual fuel combustion, where both natural gas and Diesel pilot fuel are directly injected into the cylinder at the end of the compression stroke ; (c) HCCI like combustion (PCCI, RCCI) where combustion is primarily controlled by the natural gas/Diesel fuel ratio. Although dual fuel combustion has shown significant potential it still faces some challenges, among which HC and CO emission at low load and preignition and knock at high load are the major ones.
Do Radiologists Report the TNM Staging in Radiology Reports for Head and Neck Cancers? A National Survey Study

BACKGROUND AND PURPOSE: CT and MR imaging are widely used for the staging of head and neck cancer. Currently, there are no data regarding whether the primary tumor, nodes, metastasis (TNM) staging is routinely incorporated into radiology reports. We conducted a national survey to determine whether radiologists routinely address staging, in particular regarding T (primary tumor) and N (nodal). MATERIALS AND METHODS: The survey was sent to 782 members of the American Society of Head and Neck Radiology. The survey asked whether they assign TN staging in reports. If they do assign TN staging, what are the reasons for doing so, and if not, what are the barriers or reasons for not including it in the radiology report? The method of measuring the size of the primary tumor and pathologic lymph nodes was also queried. RESULTS: A total of 229 responses were returned (29.3% response rate). Approximately half (49%; 95% confidence interval, 43.55–54.5%) of the responders thought that incorporating TN staging is important. However, only 24.5% (95% confidence interval, 19.8%–29.2%) stated that they routinely assigned TN staging in their radiology reports. The most common barriers were being afraid of being inaccurate (59%) and being unable to remember the staging classifications (58.2%); 76.9% indicated that they measure a primary tumor in 3D. CONCLUSIONS: Staging head and neck cancer based on imaging presents unique challenges. Nearly half of the responding radiologists think it is important to incorporate TN staging in radiology reports, though only a quarter of them routinely do so in practice.