Miracle-dz/UniFAR-FTUs huggingface dataset:
A diffuse‐interface modeling for liquid solution–solid gel phase transition of physical hydrogel with nonlinear deformation

A diffuse‐interface model is presented in this paper for simulation of the evolution of phase transition between the liquid solution and solid gel states for physical hydrogel with nonlinear deformation. The present domain covers the gel and solution states as well as a diffuse interface between them. They are indicated by the crosslink density in such a way that the solution phase is identified as the state when the crosslink density is small, while the gel as the state if the crosslink density becomes large. In this work, a novel order parameter is thus defined as the crosslink density, which is homogeneous in each distinct phase and smoothly varies over the interface from one phase to another. In this model, the constitutive equations, imposed on the two distinct phases and the interface, are formulated by the second law of thermodynamics, which are in the same form as those derived by a different approach. The present constitutive equations include a novel Ginzburg–Landau type of free energy with a double‐well profile, which accounts for the effect of crosslink density. The present governing equations include the equilibrium of forces, the conservations of mass and energy, and an additional kinetic equation imposed for phase transition, in which nonlinear deformation is considered. The equilibrium state is investigated numerically, where two stable phases are observed in the free energy profile. As case studies, a spherically symmetrical solution‐gel phase transition is simulated numerically for analysis of the phase transition of physical hydrogel.
Does the use of atypical antipsychotics as adjunctive therapy in depression result in cost savings? Comparing healthcare costs and utilization between second-line treatment options

Abstract Background: Several atypical antipsychotics (AAPs) are used as second-line agents for treatment resistant depression. AAPs can be expensive compared to other treatment options and can cause several side effects. Objectives: To estimate healthcare costs and utilization of AAPs compared to other second-line agents. Methods: Observational study using Medicaid claims data (2006–2011). Subjects were depression-diagnosed adult members with at least two prescriptions of antidepressant medications followed by a second-line agent. Gamma generalized linear models (GLM) produced estimates of the difference in mean expenditures among treatment groups after adjusting for individual baseline characteristics using propensity scores. Negative binomial models produced estimates of the difference in number of hospitalizations and emergency department (ED) visits. Results: A total of 3910 members received second-line treatment. Treatment groups were AAPs (n = 2211), augmentation agents other than AAPs (n = 1008), and antidepressant switching (n = 691). AAPs resulted in higher mean adjusted pharmacy costs and higher mean adjusted total mental health-related costs. Mean adjusted total healthcare costs and number of inpatient and ED visits were not different among treatments. Conclusion: The results show no evidence that AAPs used as second-line treatment for depression results in overall cost savings or lower inpatient and ED visits compared to other treatment strategies.
Ultrastructural correlates of haloperidol‐induced oral dyskinesias in rat striatum

Neuroleptics given chronically to rats induce behavioral sequelae which mimic tardive dyskinesia in some respects. The intent of this study was to investigate the ultrastructural correlates of oral dyskinesias (vacuous chewing movements [VCMs]), induced by chronic haloperidol treatment. After 6 months of treatment, rats were divided into low or high VCM groups. Rats in the high VCM group were either sacrificed on drug or were withdrawn from drug for 4 weeks. Ultrastructural analyses of the striatum indicated that synaptic density: (1) was significantly decreased in both the low and high VCM groups compared to normal controls; (2) was more profoundly decreased in the high VCM group as compared to the low VCM group; and (3) recovered to normal following drug withdrawal. Compared to controls, the density of asymmetric synapses was reduced by a similar magnitude in both the low and high VCM groups, suggesting that this change is a result of haloperidol treatment and independent of VCMs. Conversely, the density of symmetric synapses was reduced compared to normal, only in the high VCM group, suggesting that this change is specifically related to the expression of VCMs. In addition, mitochondria1 profiles were hypertrophied and less frequent in the high VCM group in comparison to controls; size, but not number, recovered following drug withdrawal. These results identify distinct ultrastructural correlates of chronic haloperidol treatment that are unique to rats that develop VCMs and suggest that these ultrastructural features may play a role in the pathophysiology of oral dyskinesias in rats. © 1995 Wiley‐Liss, Inc.
In vivo activation of the human δ-globin gene: the therapeutic potential in β-thalassemic mice

β-thalassemia and sickle cell disease are widespread fatal genetic diseases. None of the existing clinical treatments provides a solution for all patients. Two main strategies for treatment are currently being investigated: (i) gene transfer of a normal β-globin gene; (ii) reactivation of the endogenous γ-globin gene. To date, neither approach has led to a satisfactory, commonly accepted standard of care. The δ-globin gene produces the δ-globin of hemoglobin A2. Although expressed at a low level, hemoglobin A2 is fully functional and could be a valid substitute of hemoglobin A in β-thalassemia, as well as an anti-sickling agent in sickle cell disease. Previous in vitro results suggested the feasibility of transcriptional activation of the human δ-globin gene promoter by inserting a Kruppel-like factor 1 binding site. We evaluated the activation of the Kruppel-like factor 1 containing δ-globin gene in vivo in transgenic mice. To evaluate the therapeutic potential we crossed the transgenic mice carrying a single copy activated δ-globin gene with a mouse model of β-thalassemia intermedia. We show that the human δ-globin gene can be activated in vivo in a stage- and tissue-specific fashion simply by the insertion of a Kruppel-like factor 1 binding site into the promoter. In addition the activated δ-globin gene gives rise to a robust increase of the hemoglobin level in β-thalassemic mice, effectively improving the thalassemia phenotype. These results demonstrate, for the first time, the therapeutic potential of the δ-globin gene for treating severe hemoglobin disorders which could lead to novel approaches, not involving gene addition or reactivation, to the cure of β-hemoglobinopathies.
Evaluation of Methods to Detect and Characterize Antibodies against Recombinant Human Erythropoietin

Background: From May 1998 to November 2000, 13 European patients developed antibody-mediated pure red cell aplasia during treatment with recombinant human erythropoietin (rHuEPO), reinforcing the need for analytical testing for antibodies against erythropoietic agents. Specimens from 8 patients were provided for further antibody testing and characterization. Methods: We evaluated 4 analytical methods with these sera: radioimmune precipitation (RIP), enzyme-linked immunosorbent assay (ELISA), biosensor immunoassay, and a bioassay for identification of neutralizing antibodies. Results: The RIP, biosensor immunoassay, and biological assay performed equally to detect and quantify anti-rHuEPO antibodies. The ELISA failed to detect antibodies in 2 patient samples. The biosensor immunoassay could determine antibody isotypes, subclasses, and dissociation rates and the bioassay could determine whether these antibodies were able to neutralize the biological effect of the drug; the other assays could not make this determination. Conclusion: We recommend the use of the biosensor immunoassay followed by a bioassay to best identify and characterize anti-rHuEPO antibodies. The biosensor immunoassay allows for identification of all classes and subclasses of immunoglobulins and is a preferred method for the identification of lower-affinity antibodies. The bioassay is needed to determine if the antibodies identified have the capacity to neutralize a biological effect of the drug in a cell-based system.
Risk Factors for Severity and Type of the Hip Fracture

More severe hip fractures such as displaced femoral neck (FN) fractures and unstable intertrochanteric (IT) fractures lead to poorer outcomes, but risk factors for severe fractures have not been studied. To identify risk factors for severe types of hip fracture, we performed a prospective cohort study and obtained preoperative hip radiographs from women who sustained an incident hip fracture (excluding traumatic fractures). A single radiologist scored the severity of FN fractures by the Garden System: grades I and II, undisplaced; grades III and IV, displaced. The severity of IT hip fractures was rated by the Kyle System: grades I and II, stable; grades III and IV, unstable. A total of 249 women had FN fractures: 75 (30%) were undisplaced. A total of 213 women had IT fractures: 59 (28%) were stable. Both types of hip fracture increased with age, but older age was even more strongly associated with more severe hip fractures. Low BMD was more strongly related to undisplaced FN fractures (p interaction BMD × FN type, p = 0.0008) and stable IT fractures (p interaction BMD × IT type, p = 0.04). Similar findings were observed for estimated volumetric BMD and hip geometric parameters. Corticosteroid use was only associated with displaced FN fractures, and Parkinson's disease was only associated with stable IT fractures. Little difference was reported in the self‐reported circumstances surrounding each type of fracture. In conclusion, the lower the BMD, the greater the likelihood of experiencing a hip fracture that is less displaced and more stable.
The woodchuck interferon‐α system: Cloning, family description, and biologic activity

Interferon‐α (IFN‐α) is a key element in the defense against viral infection because, in addition to a direct antiviral effect, it exhibits potent immunostimulatory activity. To investigate the function of this cytokine in the woodchuck model of chronic hepatitis B, the woodchuck IFN‐α gene (IFNA) family was cloned and examined. The data indicate that this is a multigenic family from which 12 IFNA functional sequences and four pseudogene sequences were isolated. The overall identity of the amino acid sequence among the members of the woodchuck IFN‐α family is 85%, and the identity with the IFN‐α family from other species such as mice and humans is 50%. The analysis of hepatic expression of IFNA genes showed that wIFNA5a was the subtype transcribed preferentially in the woodchuck liver. The wIFNA genes transcribed in the liver were tested in an eukaryotic expression system and were found to enhance 2–5‐oligoadenylate synthetase (2–5‐OAS) mRNA levels and to posses a potent antiviral activity. Cloning of woodchuck IFNA genes will allow testing diverse forms of IFN‐α delivery as well as different combination therapies in woodchuck hepatitis virus infection, thus providing useful information for the design of new strategies for the treatment of patients with chronic hepatitis B. J. Med. Virol. 68:424–432, 2002. © 2002 Wiley‐Liss, Inc.
Diagnostic procedures after a positive spiral computed tomography lung carcinoma screen

Low‐radiation dose spiral computed tomography (LDCT) currently is being evaluated as a screening modality for lung carcinoma in a randomized trial. Although several diagnostic algorithms for the workup of positive LDCT screens have been proposed, to the authors' knowledge there is no widely accepted standard to date and there are few nationwide data concerning how such diagnostic workups are actually being performed outside a research protocol setting.
Depression, Anxiety, and Quality of Life in Paroxysmal Kinesigenic Dyskinesia Patients

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Under the condition of psychological burden, some patients’ attacks may get worsened with longer duration and higher frequency. This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population. Methods: We performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital, using Symptom Check List-90-Revised (SCL-90-R), World Health Organization Quality of Life-100 (WHOQoL-100), Self-Rating Depression Scale, and Self-Rating Anxiety Scale. We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data (taken from literature) by using the unpaired Student's t-test. We applied multivariate linear regression to analyze the relationships between motor manifestations, mental health, and quality of life among PKD patients. Results: Compared with Chinese normative data taken from literature, patients with PKD exhibited significantly higher (worse) scores across all SCL-90-R subscales (somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism; P = 0.000 for all) and significantly lower (worse) scores of five domains in WHOQoL-100 (physical domain, psychological domain, independence domain, social relationship domain, and general quality of life; P = 0.000 for all). Nonremission of dyskinesia episodes (P = 0.011) and higher depression score (P = 0.000) were significantly associated with lower levels of quality of life. The rates of depression and anxiety in patients with PKD were 41.2% (68/165) and 26.7% (44/165), respectively. Conclusions: Depression, anxiety, and low levels of quality of life were prevalent in patients with PKD. Co-occurrence of depression and anxiety was common among these patients. Regular mental health interventions could set depression and anxiety as intervention targets. Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress, and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out, intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.
Cell lineage allocation in equine blastocysts produced in vitro under varying glucose concentrations.

Equine embryos develop in vitro in the presence of high glucose concentrations, but little is known about their requirements for development. We evaluated the effect of glucose concentrations in medium on blastocyst development after ICSI. In experiment 1, there were no significant differences in rates of blastocyst formation among embryos cultured in our standard medium (DMEM/F-12), which contained >16 mM glucose, and those cultured in a minimal-glucose embryo culture medium (<1 mM; Global medium, GB), with either 0 added glucose for the first 5 days, then 20 mM (0-20) or 20 mM for the entire culture period (20-20). In experiment 2, there were no significant differences in the rates of blastocyst development (31-46%) for embryos cultured in four glucose treatments in GB (0-10, 0-20, 5-10, or 5-20). Blastocysts were evaluated by immunofluorescence for lineage-specific markers. All cells stained positively for POU5F1. An inner cluster of cells was identified that included presumptive primitive endoderm cells (GATA6-positive) and presumptive epiblast (EPI) cells. The 5-20 treatment resulted in a significantly lower number of presumptive EPI-lineage cells than the 0-20 treatment did. GATA6-positive cells appeared to be allocated to the primitive endoderm independent of the formation of an inner cell mass, as was previously hypothesized for equine embryos. These data demonstrate that equine blastocyst development is not dependent on high glucose concentrations during early culture; rather, environmental glucose may affect cell allocation. They also present the first analysis of cell lineage allocation in in vitro-fertilized equine blastocysts. These findings expand our understanding of the factors that affect embryo development in the horse.
Emdogain effect on gingival fibroblast adhesion in bioabsorbable and non-resorbable barrier membranes: An in vitro study

Background: Tissue engineering represents very exciting advances in regenerative medicine; however, periodontal literature only contains few reports. Emdogain (EMD) consists of functional molecules that have shown many advantages in regenerative treatments. This study investigated EMD effect on gingival fibroblast adhesion to different membranes. Materials and Methods: Two dense polytetrafluoroethylene membranes (GBR-200, TXT-200), Alloderm and a collagenous membrane (RTM Collagen) were used in this experimental study. Each membrane was cut into four pieces and placed at the bottom of a well in a 48-well plate. 10 μg/mL of EMD was added to two wells of each group. Two wells were left EMD free. Gingival fibroblasts were seeded to all the wells. Cell adhesion was evaluated by means of a Field Emission Scanning Electron Microscope after 24 hours incubation. Data was analyzed by independent t-test, one-way and two-way ANOVA and post hoc LSD test. P < 0.05 in independent t-test analysis and P < 0.001 in one-way ANOVA, two-way ANOVA and post hoc LSD analysis was considered statistically significant. Results: Alloderm had the highest cell adhesion capacity in EMD+ group and the difference was statistically significant (P < 0.001). In EMD- group, cell adhesion to TXT-200 and Alloderm was significantly higher than GBR-200 and collagenous membrane (P < 0.001). Conclusion: This study showed that EMD may decrease the cell adhesion efficacy of GBR-200, TXT-200 and collagenous membrane but it can promote this efficacy in Alloderm. It also showed the composition of biomaterials, their surface textures and internal structures can play an important role in their cell adhesion efficacy.
Human Hepatic Lipase Subunit Structure Determination*

Chinese hamster ovary cells were stably transfected with a human hepatic lipase (HL) cDNA. The recombinant enzyme was purified from culture medium in milligram quantities and shown to have a molecular weight, specific activity, and heparin affinity equivalent to HL present in human post-heparin plasma. The techniques of intensity light scattering, sedimentation equilibrium, and radiation inactivation were employed to assess the subunit structure of HL. For intensity light scattering, purified enzyme was subjected to size exclusion chromatography coupled to three detectors in series: an ultraviolet absorbance monitor, a differential refractometer, and a light scattering photometer. The polypeptide molecular weight (without carbohydrate contributions) was calculated using the measurements from the three detectors combined with the extinction coefficient of human HL. A single protein peak containing HL activity was identified and calculated to have a molecular mass of 107,000 in excellent agreement with the expected value for a dimer of HL (106.8 kDa). In addition, sedimentation equilibrium studies revealed that HL had a molecular mass (with carbohydrate contributions) of 121 kDa. Finally, to determine the smallest structural unit required for lipolytic activity, HL was subjected to radiation inactivation. Purified HL was exposed to various doses of high energy electrons at −135°C; lipase activity decreased as a single exponential function of the radiation dose to less than 0.01% remaining activity. The target size of functional HL was calculated to be 109 kDa, whereas the size of the structural unit was determined to be 63 kDa. These data indicate that two HL monomer subunits are required for lipolytic activity, consistent with an HL homodimer. A model for active dimeric hepatic lipase is presented with implications for physiological function.
Dominant‐negative mutants of a yeast G‐protein beta subunit identify two functional regions involved in pheromone signalling.

The STE4 gene, which encodes the beta subunit of the mating response G‐protein in the yeast Saccharomyces cerevisiae, was subjected to a saturation mutagenesis using ‘doped’ oligodeoxynucleotides. We employed a genetic screen to select dominant‐negative STE4 mutants, which when overexpressed from the GAL1 promoter, interfered with the signalling function of the wild type protein. The identified inhibitory amino acid alterations define two small regions that are crucially involved in transmitting the mating signal from G beta to downstream components of the signalling pathway. These results underline the positive signalling role of yeast G beta and assign for the first time the positive signalling function of a G‐protein beta subunit to specific structural features.
Effects of Combined Exercise Training on Body Composition and Metabolic Syndrome Factors

Background: Metabolic syndrome (MS) is emerging as a serious public health problem in Korea. The purpose of this study was to examine the effects of 12 weeks of combined exercise training on body composition and MS factors in obese Korean female college students. Methods: Subjects were randomly assigned to exercise (n = 7) and control (n = 9) groups. The exercise group trained for 80 min/day, for 3 day/week for 12 weeks. Each exercise session comprised 3 phases: warm-up for 10 min, main exercise for 60 min (consisting of aerobic exercise for 30 min and resistance exercise for 30 min), and cool down for 10 min. Results: The exercise intensity for aerobic exercise was 60–80% of the heart rate reserve (HRR) for 30 min, while the resistance exercises were 10–15 repetitions maximum (RM) for 30 min. Two-way repeated analysis of variance (ANOVA) was used for statistical analysis. There were no interaction effects (time × group) on the MS-related factors of blood lipid composition such as triglycerides (TGs), high-density lipoprotein (HDL), glucose, total cholesterol (TC), and low-density lipoprotein (LDL). However, interaction effects were observed (time × group) on percent body fat (P = 0.006), waist circumference (WC; P < 0.001), systolic blood pressure (SBP; P = 0.010), and diastolic blood pressure (DBP; P = 0.007). Conclusions: A 12-week supervised combined exercise program could effectively reduce percent body fat, WC, SBP, and DBP. However, it was not effective on MS-related factors of blood lipid composition such as TG, HDL, glucose, TC, and LDL in a sample population of obese Korean female college students.