Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissolution Rate Enhancement and Physicochemical Characterization of Artemether and Lumefantrine Solid Dispersions

The current study was conceded out with a vision to enhance solubility and thereby dissolution rate of poorly water soluble Artemether [ARTM] and Lumefantrine [LUM] [BCS-class IV drugs] using Lutrol F127 as carrier surfactant. It’s difficult to choose a single carrier which forms solid dispersion [SD] with both the drugs by melt method. For which number of polymers and combination trials were carried out and finally Lutrol F127 was selected for further studies. SD was prepared by melt method using different ratios of drug and Lutrol F127. Saturation solubility study was conducted to evaluate the effect of polymer on aqueous solubility of ARTM and LUM. Solid state characterization was evaluated by fourier transformation infrared spectroscopy, differential scanning calorimetry, x-ray diffraction study and scanning electron microscopy. In vitro dissolution study was performed in phosphate buffer at pH 7.2 [with 1% SLS] and 0.1 N HCl [with 2% Benzalkonium chloride, BKC] for ARTM and LUM respectively. Solid state study showed partial interaction between drug and Lutrol F127. In vitro dissolution rate of ARTM and LUM from SD was signiﬁcantly higher compared to pure drug. The dissolution rate of SD prepared by melt method was found to be higher than that of pure drugs and their physical mixtures. Thus, SD using melt method can be successfully used for the improvement of the dissolution rate of ARTM and LUM.
Stability and uniqueness of $p$-values for likelihood-based inference

Likelihood-based methods of statistical inference provide a useful general methodology that is appealing, as a straightforward asymptotic theory can be applied for their implementation. It is important to assess the relationships between different likelihood-based inferential procedures in terms of accuracy and adherence to key principles of statistical inference, in particular those relating to conditioning on relevant ancillary statistics. An analysis is given of the stability properties of a general class of likelihood-based statistics, including those derived from forms of adjusted profile likelihood, and comparisons are made between inferences derived from different statistics. In particular, we derive a set of sufficient conditions for agreement to $O_{p}(n^{-1})$, in terms of the sample size $n$, of inferences, specifically $p$-values, derived from different asymptotically standard normal pivots. Our analysis includes inference problems concerning a scalar or vector interest parameter, in the presence of a nuisance parameter.
Portable gas analyser Cosmed K4b2 compared to a laboratory based mass spectrometer system.

AIM The purpose of this study was to systematically test the accuracy of an automated, portable, gas analysis system, the Cosmed K4b2 with a laboratory based mass spectrometer system, the Morgan EX670 across a number of gas and ventilation parameters. METHODS Eight subjects (mean+/-SE) age, 23.7+/-1.1 y, height, 1.78+/-0.01 m, mass, 74.4+/-2.1 kg performed a V.O2max test and a submaximal exercise test at 150, 200, 250 and 300 Watts (W), on an SRM cycle ergometer. The Morgan EX670 system and the K4b2 were randomly connected in series, using the same breath for the calculation of gas and ventilatory parameters. RESULTS The K4b2 system reads significantly higher than the Morgan EX 670 for both VO2 and V.CO2 at 250 (VO2/V.CO2: p<0.05, p<0.002), and 300 W (VO2/V.CO2: p<0.002, p<0.005). Unsystematic bias between the 2 analysers varies between 1% and 16% and systematic bias between 3% and 8%. CONCLUSION There are some significant unsystematic and systematic differences between these 2 systems and laboratories should endeavour to utilise either one or the other piece of equipment to test their subjects.
Multivariate Filter Estimation of Potential Output for the Euro Area and the United States

Estimates of potential output are an important component of a structured forecasting and policy analysis system. Using information on consensus forecasts, this paper extends the multivariate filter developed by Laxton and Tetlow (1992) and modified by Benes and others (2010) and Blagrave and others (2015). We show that, although still fairly uncertain, the real time estimates from this approach are more accurate relative to those of naive univariate statistical filters. The paper presents estimates for the euro area and the United States and discusses how the filtered estimates at the end of the sample period can be improved with additional information.
Source monitoring.

A framework for understanding source monitoring and relevant empirical evidence is described, and several related phenomena are discussed: old-new recognition, indirect tests, eyewitness testimony, misattributed familiarity, cryptomnesia, and incorporation of fiction into fact. Disruptions in source monitoring (e.g., from confabulation, amnesia, and aging) and the brain regions that are involved are also considered, and source monitoring within a general memory architecture is discussed. It is argued that source monitoring is based on qualities of experience resulting from combinations of perceptual and reflective processes, usually requires relatively differentiated phenomenal experience, and involves attributions varying in deliberateness. These judgments evaluate information according to flexible criteria and are subject to error and disruption. Furthermore, diencephalic and temporal regions may play different roles in source monitoring than do frontal regions of the brain.
CaV1.2 Channel N-terminal Splice Variants Modulate Functional Surface Expression in Resistance Size Artery Smooth Muscle Cells*

Voltage-dependent Ca2+ (CaV1.2) channels are the primary Ca2+ influx pathway in arterial smooth muscle cells and are essential for contractility regulation by a variety of stimuli, including intravascular pressure. Arterial smooth muscle cell CaV1.2 mRNA is alternatively spliced at exon 1 (e1), generating e1b or e1c variants, with e1c exhibiting relatively smooth muscle-specific expression in the cardiovascular system. Here, we examined physiological functions of CaV1.2e1 variants and tested the hypothesis that targeting CaV1.2e1 modulates resistance size cerebral artery contractility. Custom antibodies that selectively recognize CaV1.2 channel proteins containing sequences encoded by either e1b (CaV1.2e1b) or e1c (CaV1.2e1c) both detected CaV1.2 in rat and human cerebral arteries. shRNA targeting e1b or e1c reduced expression of that CaV1.2 variant, induced compensatory up-regulation of the other variant, decreased total CaV1.2, and reduced intravascular pressure- and depolarization-induced vasoconstriction. CaV1.2e1b and CaV1.2e1c knockdown reduced whole cell CaV1.2 currents, with CaV1.2e1c knockdown most effectively reducing total CaV1.2 and inducing the largest vasodilation. Knockdown of α2δ-1, a CaV1.2 auxiliary subunit, reduced surface expression of both CaV1.2e1 variants, inhibiting CaV1.2e1c more than CaV1.2e1b. e1b or e1c overexpression reduced CaV1.2 surface expression and whole cell currents, leading to vasodilation, with e1c overexpression inducing the largest effect. In summary, data indicate that arterial smooth muscle cells express CaV1.2 channels containing e1b or e1c-encoded N termini that contribute to CaV1.2 surface expression, α2δ-1 preferentially traffics the CaV1.2e1c variant to the plasma membrane, and targeting of CaV1.2e1 message or the CaV1.2 channel proximal N terminus induces vasodilation.
Socioterritorial Units among Carnivores and Early Hominids

It is argued that one form of socioterritorial organization is most common among the larger social carnivores and may be optimal under most conditions. This form of organization is based on a stable territorial group with the capacity to disperse into independent subgroups and yet retain its identity. The importance of such a unit among hyenas, lions, and wolves is documented. By analogy, the earliest hominid big-game hunters may have been organized in much the same way. This view is consistent with other evidence for early hominid socioterritorial organization, derived from observations on chimpanzees and human hunters.
Ecomycins, unique antimycotics from Pseudomonas viridiflava

A novel family of peptide antimycotics, termed ecomycins, is described from Pseudomonas viridiflava, a plant‐associated bacterium. Ecomycins B and C have molecular masses of 1153 and 1181. They contain equimolar amounts of a β hydroxyaspartic acid, homoserine, threonine, serine, alanine, glycine and one unknown amino acid. Fatty acids were detectable after hydrolysis, methylation and gas chromatography and mass spectroscopy. The ecomycins have significant bioactivities against a wide range of human and plant pathogenic fungi. The minimum inhibitory concentration values for ecomycin B were 4·0 μg ml−1 against Cryptococcus neoformans and 31 μg ml−1 against Candida albicans. Pseudomonas viridiflava also produces what appears to be syringotoxin, an antifungal lipopeptide previously described from Ps. syringae.
Effect of sorghum particle size on digestibility of nutrients at the terminal ileum and over the total digestive tract of growing-finishing pigs.

The effect of sorghum particle size on nutrient digestibilities at the terminal ileum and over the total digestive tract of growing-finishing pigs were investigated in a replicated 3 X 3 Latin square trial. Sorghum-casein diets were used. Sorghum was dry rolled (C) or ground in a hammer mill through 6.4 mm (M) or 3.2 mm (F) screens, producing particles with a modulus of fineness of 3.57, 2.85 or 2.36, respectively. Each successive reduction in particle size improved (P less than .05) the apparent ileal digestibility of dry matter, starch, gross energy and N. Measured over the total digestive tract, digestibilities of these components were highest (P less than .05) for the F diet but they did not differ (P greater than .10) between diets M and C because of increased (P less than .05) disappearance in the large intestine of dry matter, starch and gross energy from the C diet. N loss in the large intestine was also higher for pigs fed diet C than for those fed diet M, but the difference was not significant. The digestibilities of most amino acids at the terminal ileum were improved (P less than .05) as particle size decreased. Lysine digestibilities were not affected (P greater tha .10). Amino acid digestibilities measured over the total digestive tract were consistently higher (P less than .05) for diet F than diets M and C, which did not differ (P greater than .10) from one another. A comparison of ileal and total tract digestibilities indicated a net disappearance of all measured amino acids except lysine during large intestine transit. These data indicate that increasing fineness of grind will improve digestibility of nutrients in sorghum by growing-finishing pigs.
Behavioral and psychological symptoms and the progression of dementia of the Alzheimer type in nursing home residents.

BACKGROUND Behavioral and psychological symptoms are common in the course of dementia of the Alzheimer's type (DAT). Some behavioral and psychological symptoms may be predictors of the progression of dementia and cognitive impairment in DAT. However, studies on this topic face serious methodological problems. The aim of our study was to investigate how aggressive and impulsive behaviors correlate with the progression of dementia and related cognitive impairments in DAT patients. MATERIAL/METHODS Using the Cohen-Mansfield Agitation Inventory (CMAI) and the ADAS-cog we examined 39 nursing home residents diagnosed with mild to moderate DAT. Of these participants, 26 were re-evaluated with the ADAS-cog two years after baseline. RESULTS Aggressive and impulsive behaviors correlated with the degree of cognitive impairment. However, we also found that particular ADAS-cog items correlated differently with the CMAI score. Moreover, various CMAI categories were differently related to cognitive disorders. Impairments in cognitive functioning best explain the fluctuations of verbal aggression and physical agitation (non-aggressive). At baseline, the more demented subjects had a higher general score on the CMAI scale and showed greater rates of physical aggression, verbal aggression and non-aggressive physical agitation. CONCLUSIONS Particular items of the CMAI scale significantly differentiated our subjects in terms of progression of cognitive impairment. Aggressive behaviors in patients with DAT are linked to both the severity of dementia and the rate of its progression. At the same time, significant differences were noted with respect to particular behaviors.
Mechanism of ginsenoside Rg1 renal protection in a mouse model of d-galactose-induced subacute damage

Abstract Context Ginseng is a widely used herbal medicine in China but its mechanism of action remains unclear. Objective The objectives of this work were to study the protective effect of ginsenoside Rg1 on subacute murine renal damage induced by d-galactose and its mechanism. Materials and methods C57BL/6J mice were injected with 120 mg/kg/d (sc) d-galactose for 1 week, followed by a combined treatment of Rg1 20 mg/kg/d (ip) and 120 mg/kg/d d-galactose (sc) for 5 weeks. Mice were injected with the 0.9% saline 0.2 mL/d (sc) and 120 mg/kg/d d-galactose (sc) for 6 weeks in the control group and the d-galactose group, respectively. After 6 weeks, urea, creatinine, uric acid, cystatin (Cys-C), senescence-associated β-galactosidase (SA-β-gal) staining positive kidney cells, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), glycation end products (AGEs) and 8-hydroxy-2 deoxyguanosine (8-OH-dG) were measured. Results Treatment with Rg1 ameliorated kidney function and aging state (urea from 17.19 ± 1.09 to 15.77 ± 1.22 mmol·L − 1, creatinine from 29.40 ± 5.72 to 22.60 ± 3.97 μmol·L − 1, uric acid from 86.80 ± 5.97 to 72.80 ± 10.61 μmol·L − 1, Cys-C from 0.23 ± 0.03 to 0.18 ± 0.05 mg·L − 1, ROD of SA-β-gal from 56.32 ± 10.48 to 26.78 ± 7.34, SOD from 150.22 ± 19.07 to 190.56 ± 15.83 U·(mg·prot) −1, MDA from 9.28 ± 1.59 to 3.17 ± 0.82 nmol·(mg·prot) −1, GSH-PX from 15.68 ± 2.11 to 20.32 ± 2.96 U·(mg·prot) −1 as well as regulated glomerulus morphology (glomerulus diameter from 775.77 ± 18.41 to 695.04 ± 14.61 μm, renal capsule width from 39.56 ± 3.51 to 31.42 ± 2.70 μm, glomerulus basement membrane from 206.03 ± 16.22 to 157.27 ± 15.70 nm, podocyte slit from 55.21 ± 8.55 to 37.63 ± 6.65 nm). Conclusions Ginsenoside Rg1 can antagonise d-galactose subacute renal damage in mice and this may occur due to alleviating oxidative stress injury.
The Clinical Significance of a Negative Loop Electrosurgical Cone Biopsy for High-Grade Dysplasia

OBJECTIVE: We sought to estimate the incidence and clinical significance of a negative therapeutic loop electrosurgical excision procedure (LEEP) and to evaluate patient specimens for limiting histologic features associated with a negative LEEP. METHODS: We identified 674 patients with biopsy-confirmed high-grade cervical dysplasia who were treated with LEEP from 1991 through 2001. The results of these LEEP procedures were reviewed for the absence of dysplasia or the presence of cervical intraepithelial neoplasia stages 1–3. Computerized pathology files of patients were then reviewed through July 2002 to determine whether dysplasia recurred. Slides of negative LEEP specimens were reviewed to confirm the absence of dysplasia and to search for histologic features that may have limited our interpretation of the specimen. RESULTS: Ninety-three (14%) of LEEP specimens reviewed were completely negative for dysplasia. Clinical follow-up was available on 75 of the 93 patients, with a median follow-up time of 2 years. Eighteen (24%) patients had subsequent positive follow-up, including carcinoma (n = 2), high-grade squamous intraepithelial lesions (n = 8), low-grade squamous intraepithelial lesion (n = 6), and atypical squamous cells of undetermined significance (n = 2). Patients with negative LEEPs had a recurrence rate similar to patients with positive LEEPs (24% versus 27%). Limiting histologic features were more commonly identified in negative LEEPs as compared with LEEPs containing dysplasia (16% versus 5%, P < .001). CONCLUSION: A negative LEEP is not an uncommon finding, occurring in 14% (95% confidence interval 11–17%) of specimens at our institution. Negative LEEPs are more likely to contain histologic features that limit pathology interpretation. A negative LEEP is not a reassuring finding and was associated with a recurrence rate similar to those of a positive LEEP. Both negative and positive populations should be carefully followed. LEVEL OF EVIDENCE: II-3
Long‐term outcome of highly sensitized African American patients transplanted with deceased donor kidneys

Undertaking transplantation in highly sensitized African American (AA) patients as transplant recipients represents a unique challenge. We retrospectively compared the outcomes of AA with non‐African American (NAA) patients who had panel reactive antibody >80% and received deceased donor (DD) kidneys by virtual crossmatch. Immunosuppressive regimen included basiliximab induction and tacrolimus, mycophenolate acid and steroids maintenance. Among 835 consecutive transplants from 1998 to 2007, 142 (17%) were sensitized patients including 89 (16.6%) AA and 53 (17.7%) NAA patients. The AA group had similar 5‐year incidence of acute rejection as NAA group (21.4% vs. 26.4%, P = 0.25). Kaplan–Meier estimated graft survival at 1, 3 and 5 years were 91%, 85% and 82% in AA group, and 94%, 79% and 71% in NAA group (P = 0.08). The death‐censored graft survival at 1, 3, and 5 years were 93%, 86% and 84% in AA group, and 96%, 83% and 78% in NAA group (P = 0.11). The 1, 3, and 5 years patient survivals were 93%, 88% and 85% in AA group, and 96%, 96% and 94% in NAA group (P = 0.17). Highly sensitized AA patients could be transplanted with DD kidneys at a similar rate as NAA patients, and they may not have a higher incidence of rejection or an inferior graft survival than NAA patients.
Multiple phosphorylation of Rad9 by CDK is required for DNA damage checkpoint activation

The DNA damage checkpoint controls cell cycle arrest in response to DNA damage, and activation of this checkpoint is in turn cell cycle-regulated. Rad9, the ortholog of mammalian 53BP1, is essential for this checkpoint response and is phosphorylated by the cyclin-dependent kinase (CDK) in the yeast Saccharomyces cerevisiae. Previous studies suggested that the CDK consensus sites of Rad9 are important for its checkpoint activity. However, the precise CDK sites of Rad9 involved have not been determined. Here we show that CDK consensus sites of Rad9 function in parallel to its BRCT domain toward checkpoint activation, analogous to its fission yeast ortholog Crb2. Unlike Crb2, however, mutation of multiple rather than any individual CDK site of Rad9 is required to completely eliminate its checkpoint activity in vivo. Although Dpb11 interacts with CDK-phosphorylated Rad9, we provide evidence showing that elimination of this interaction does not affect DNA damage checkpoint activation in vivo, suggesting that additional pathway(s) exist. Taken together, these findings suggest that the regulation of Rad9 by CDK and the role of Dpb11 in DNA damage checkpoint activation are more complex than previously suggested. We propose that multiple phosphorylation of Rad9 by CDK may provide a more robust system to allow Rad9 to control cell cycle-dependent DNA damage checkpoint activation.
Slow disappearance of peripheral blast cells: an independent risk factor indicating poor prognosis in children with acute lymphoblastic leukemia.

The aim of this study was to find out whether the time required for disappearance of peripheral blast cells, or blast clearance, could be used to identify patients with a slow response to treatment associated with a poor prognosis of acute lymphoblastic leukemia (ALL). Our series consisted of 158 children with newly diagnosed ALL. The mean follow-up time was 69 months (range 22 to 140 months). Blast clearance was significantly associated with length of event-free survival. Only two of nine children with blast clearance greater than or equal to 2 weeks and 4 of 11 children with blast clearance of 11 to 13 days were in remission at the time of analysis as compared with 86 of 138 of the children with more rapid blast clearance. The respective 5-year event-free survivals were 17%, 36%, and 60% (P = .003). Multivariate analysis showed that the relative risk of death or relapse in patients with blast clearance of greater than 10 days was 5.2-fold (95% confidence limits 2.1 to 13.1) as compared with the others (P less than .001). Our results indicate that patients with a slow response to treatment can be identified by simple differential peripheral cell counts during the early induction phase well before or even instead of performance of a more invasive bone marrow aspiration.
Programmed Death-1 (PD-1) is a Marker of Germinal Center-associated T Cells and Angioimmunoblastic T-Cell Lymphoma

Programmed death-1 (PD-1), a member of the CD28 costimulatory receptor family, is expressed by germinal center-associated T cells in reactive lymphoid tissue. In a study of a wide range of lymphoproliferative disorders, neoplastic T cells in 23 cases of angioimmunoblastic lymphoma were immunoreactive for PD-1, but other subtypes of T cell and B cell non-Hodgkin lymphoma, as well as classic Hodgkin lymphoma, did not express PD-1. The pattern of PD-1 immunostaining of neoplastic cells in angioimmunoblastic lymphoma was similar to that reported for CD10, a recently described marker of neoplastic T cells in angioimmunoblastic lymphoma. Tumor-associated follicular dendritic cells in cases of angioimmunoblastic lymphoma were found to express PD-L1, the PD-1 ligand. In addition, PD-1-positive reactive T cells formed rosettes around neoplastic L&H cells in 14 cases of nodular lymphocyte predominant Hodgkin lymphoma studied. These findings, along with data from previous studies, suggest that angioimmunoblastic lymphoma is a neoplasm of germinal center-associated T cells and that there is an association of germinal center-associated T cells and neoplastic cells in nodular lymphocyte predominant Hodgkin lymphoma. PD-1 is a useful new marker for angioimmunoblastic lymphoma and lends further support to a model of T-cell lymphomagenesis in which specific subtypes of T cells may undergo neoplastic transformation and result in specific, distinct histologic, immunophenotypic, and clinical subtypes of T-cell neoplasia.
Symptoms of PTSD among Children Living in War Zones in Same Cultural Context and Different Situations

Situations of war and military conflict have been linked to the development of PostTraumatic Stress Disorder (PTSD). To our knowledge, there are no studies that have examined, within the same conflict and the same culture, exposure to different traumatic events or traumatic events of different intensity. The aim of this study was to evaluate the symptoms of PTSD among Palestinian schoolchildren in two different areas of Hebron. A total of 381 schoolchildren from different parts of Hebron participated in the study. To evaluate the symptoms of PTSD, the children were asked to complete the Child Post Traumatic Stress Reaction Index. To evaluate the traumatic events experienced, they completed the Gaza Traumatic Event Checklist. Results indicate that 77.4% of the children living in Hebron show symptoms of moderatetosevere PTSD, and 20.5% of them meet the DSMIV diagnostic criteria for chronic PTSD. There were no significant differences in total symptoms between the two areas of Hebron, but there were differences within the specific types of symptoms. It is clear that the traumatic events of the war lead to the development of posttraumatic stress in children and that psychological intervention