Miracle-dz/UniFAR-FTUs huggingface dataset:
A cessation program for snuff-dippers with long-term, extensive exposure to Swedish moist snuff: A 1-year follow-up study

Abstract Objective. Smokeless tobacco (Swedish moist ‘snus’) users are often strongly addicted to nicotine. Compared to the large number of smoking-cessation studies, there have been few evaluated clinical cessation programs in conjunction with nicotine replacement therapy (NRT). The aim of this study was to evaluate a cessation program for snus users with a weekly use of >2 cans/week for >10 years. Material and methods. A prospective, open, non-randomized intervention trial was undertaken including baseline oral examination and soft tissue biopsy, minor physical examination, brief cessation advice, NRT recommendations and five prospective follow-up visits within 12 months. Individual cessation counseling was given, together with oral examination in the dental office. Fifty snus users with a minimum consumption of 100 g/week who were actively seeking cessation treatment were recruited through advertising. Self-reported abstaining, including random-sample biochemical verification, and NRT use were evaluated at 6 weeks and 3, 6 and 12 months. Results. At the 3-, 6- and 12-month visits, 58%, 46% and 30% of subjects, respectively were tobacco-abstinent. All nicotine abstinence was randomly controlled during the study except at 12 months, where all subjects claiming abstinence were confirmed biochemically and clinically. Conclusion. Smokeless tobacco cessation achieved together with suitable NRT seems a promising way to improve a persistent tobacco-free condition.
Serum Bilirubin and Carbohydrate Antigen 19-9 Levels as Predictors of Malignancy in Obstructive Jaundice – A Retrospective Analysis

Background: Obstructive jaundice due to malignant pathology is often associated with high bilirubin levels. This may not always be true as malignant pathologies can still present with low bilirubin levels in the early stages or benign pathologies can present with high levels if there is associated cholangitis. Also, Carbohydrate Antigen (CA19-9) has been an unreliable predictor of malignancy. Aim and Objectives: Our study examined the combined accuracy of bilirubin levels and CA19-9, in order to predict malignancy as a cause of obstructive jaundice. Material and Methods: Bilirubin levels in a total of 900 patients with obstructive jaundice were analyzed over a period of 5 years in a retrospective study. CA 19-9 levels were also analyzed in those patients suspected to have malignancy on clinical evaluation or imaging (649 patients). The values of bilirubin in isolation and with CA19-9 in combination were used for co relation, along with imaging and histopathology. Results: Bilirubin levels in isolation, as a predictor of pathology in patients with obstructive jaundice were highly significant (Area under Curve =0.805; P < 0.01). Bilirubin level >7 mg% provided the optimum combined sensitivity and specificity for malignancy (71.9% and 84.9%, respectively). The application of a bilirubin level > 19 mg% achieved specificity of 99.1% for malignancy. The sensitivity and specificity of CA 19-9 in isolation was 70.9% and 78.3% respectively at a cut-off value of 37U/ml. In combination, the sensitivity and the specificity were 87.9% and 91.3% respectively. Conclusion: Serum bilirubin and CA 199 levels are routinely done as a part of the patients workup for obstructive jaundice. When evaluated in combination the positive predictive value increases Serum Bilirubin and Carbohydrate Antigen 19-9 Levels as Predictors of Malignancy in Obstructive Jaundice – A Retrospective Analysis 1* 1 1 1 1 Devbrata R. Adhikari , Hozefa Lokhandwala , Bhushan Thombare , Ketki Gharpure , Rajinder Singh ,
Tautomerism, acid‐base equilibria, and H‐bonding of the six histidines in subtilisin BPN′ by NMR

We have determined by 15N, 1H, and 13C NMR, the chemical behavior of the six histidines in subtilisin BPN′ and their PMSF and peptide boronic acid complexes in aqueous solution as a function of pH in the range of from 5 to 11, and have assigned every 15N, 1H, Cε1, and Cδ2 resonance of all His side chains in resting enzyme. Four of the six histidine residues (17, 39, 67, and 226) are neutrally charged and do not titrate. One histidine (238), located on the protein surface, titrates with pKa = 7.30 ± 0.03 at 25°C, having rapid proton exchange, but restricted mobility. The active site histidine (64) in mutant N155A titrates with a pKa value of 7.9 ± 0.3 and sluggish proton exchange behavior, as shown by two‐site exchange computer lineshape simulation. His 64 in resting enzyme contains an extremely high Cε1‐H proton chemical shift of 9.30 parts per million (ppm) owing to a conserved Cε1‐H…O=C H‐bond from the active site imidazole to a backbone carbonyl group, which is found in all known serine proteases representing all four superfamilies. Only His 226, and His 64 at high pH, exist as the rare Nδ1‐H tautomer, exhibiting 13Cδ1 chemical shifts ∼9 ppm higher than those for Nε2‐H tautomers. His 64 in the PMSF complex, unlike that in the resting enzyme, is highly mobile in its low pH form, as shown by 15N‐1H NOE effects, and titrates with rapid proton exchange kinetics linked to a pKa value of 7.47 ± 0.02.
Effectiveness of the Antenatal Psychosocial Health Assessment (ALPHA) form in detecting psychosocial concerns: a randomized controlled trial

Background: A pregnant woman's psychological health is a significant predictor of postpartum outcomes. The Antenatal Psychosocial Health Assessment (ALPHA) form incorporates 15 risk factors associated with poor postpartum outcomes of woman abuse, child abuse, postpartum depression and couple dysfunction. We sought to determine whether health care providers using the ALPHA form detected more antenatal psychosocial concerns among pregnant women than providers practising usual prenatal care. Methods: A randomized controlled trial was conducted in 4 communities in Ontario. Family physicians, obstetricians and midwives who see at least 10 prenatal patients a year enrolled 5 eligible women each. Providers in the intervention group attended an educational workshop on using the ALPHA form and completed the form with enrolled women. The control group provided usual care. After the women delivered, both groups of providers identified concerns related to the 15 risk factors on the ALPHA form for each patient and rated the level of concern. The primary outcome was the number of psychosocial concerns identified. Results were controlled for clustering. Results: There were 21 (44%) providers randomly assigned to the ALPHA group and 27 (56%) to the control group. A total of 227 patients participated: 98 (43%) in the ALPHA group and 129 (57%) in the control group. ALPHA group providers were more likely than control group providers to identify psychosocial concerns (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1–3.0; p = 0.02) and to rate the level of concern as “high” (OR 4.8, 95% CI 1.1–20.2; p = 0.03). ALPHA group providers were also more likely to detect concerns related to family violence (OR 4.8, 95% CI 1.9–12.3; p = 0.001). Interpretation: Using the ALPHA form helped health care providers detect more psychosocial risk factors for poor postpartum outcomes, especially those related to family violence. It is a useful prenatal tool, identifying women who would benefit from additional support and interventions.
Training Conditional Random Fields with Multivariate Evaluation Measures

This paper proposes a framework for training Conditional Random Fields (CRFs) to optimize multivariate evaluation measures, including non-linear measures such as F-score. Our proposed framework is derived from an error minimization approach that provides a simple solution for directly optimizing any evaluation measure. Specifically focusing on sequential segmentation tasks, i.e. text chunking and named entity recognition, we introduce a loss function that closely reflects the target evaluation measure for these tasks, namely, segmentation F-score. Our experiments show that our method performs better than standard CRF training.
Using text search for personal photo collections with the MediAssist system

The MediAssist system enables organisation and searching of personal digital photo collections based on contextual information, content-based analysis and semi-automatic annotation. One mode of user interaction uses automatically extracted features to create text surrogates for photos, which enables text search of photo collections without manual annotation. Our evaluation shows that this text search facility is effective for known-item search.
Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix

Necdin is expressed predominantly in terminally differentiated neurons, and its ectopic expression suppresses cell proliferation. We screened a cDNA library from neurally differentiated embryonal carcinoma P19 cells for necdin‐binding proteins by the yeast two‐hybrid assay. One of the positive clones contained cDNA encoding a carboxyl‐terminal portion of heterogeneous nuclear ribonucleoprotein U (hnRNP U), a nuclear matrix‐associated protein that interacts with chromosomal DNA. We isolated cDNA encoding full‐length mouse hnRNP U to analyze its physical and functional interactions with necdin. The necdin‐binding site of hnRNP U was located near a carboxyl‐terminal region that mediated the association between hnRNP U and the nuclear matrix. In postmitotic neurons, endogenously expressed necdin and hnRNP U were detected in the nuclear matrix and formed a stable complex. Ectopically expressed necdin was concentrated in the nucleoli, but coexpressed hnRNP U recruited necdin to the nucleoplasmic compartment of the nuclear matrix. Furthermore, under the same conditions necdin and hnRNP U cooperatively suppressed the colony formation of transfected SAOS‐2 cells. These results suggest that necdin suppresses cell proliferation through its interaction with hnRNP U in the specific subnuclear structure. J. Cell. Biochem. 84: 545–555, 2002. © 2001 Wiley‐Liss, Inc.
Hollow superparamagnetic PLGA/Fe 3O 4 composite microspheres for lysozyme adsorption

Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe3O4 composite microspheres composed of an inner cavity, PLGA inner shell and Fe3O4 outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe3O4 nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g−1) and high efficiency in lysozyme adsorption.
Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from the Flower of Jatropha integerrima by Response Surface Methodology

An ultrasound-assisted extraction (UAE) method was developed for the efficient extraction of natural antioxidants from the flowers of Jatropha integerrima. Four independent variables, including ethanol concentration, solvent/material ratio, ultrasound irradiation time and temperature were studied by single factor experiments. Then, the central composite rotatable design and response surface methodology were employed to investigate the effect of three key parameters (ethanol concentration, solvent/material ratio, and ultrasound irradiation time) on the antioxidant activities of the flower extracts. The optimal extraction conditions were an ethanol concentration of 59.6%, solvent/material ratio of 50:1, ultrasound irradiation time of 7 min, and ultrasound irradiation temperature of 40 °C. Under these conditions, the optimized experimental value was 1103.38 ± 16.11 µmol Trolox/g dry weight (DW), which was in accordance with the predicted value (1105.49 µmol Trolox/g DW). Furthermore, the antioxidant activities of flower extracts obtained by UAE were compared with those produced by the traditional maceration and Soxhlet extraction methods, and UAE resulted in higher antioxidant activities after a shorter time at a lower temperature. The results obtained are helpful for the full utilization of Jatropha integerrima, and also indicate that ultrasound-assisted extraction is an efficient method for the extraction of natural antioxidants from plant materials.
Induced Pluripotent Stem Cell Derived Macrophages as a Cellular System to Study Salmonella and Other Pathogens

A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (Mφs) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established Mφ-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-γ and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds.
Looking at cell mechanics with atomic force microscopy: Experiment and theory

This review reports on the use of the atomic force microscopy in the investigation of the mechanical properties of cells. It is shown that the technique is able to deliver information about the cell surface properties (e.g., topography), the Young modulus, the viscosity, and the cell the relaxation times. Another aspect that this short review points out is the utilization of the atomic force microscope to investigate basic questions related to materials physics, biology, and medicine. The review is written in a chronological way to offer an overview of phenomenological facts and quantitative results to the reader. The final section discusses in detail the advantages and disadvantages of the Hertz and JKR models. A new implementation of the JKR model derived by Dufresne is presented. Microsc. Res. Tech. 77:947–958, 2014. © 2014 Wiley Periodicals, Inc.
Aberrant 5′ splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization

Despite a growing number of splicing mutations found in hereditary diseases, utilization of aberrant splice sites and their effects on gene expression remain challenging to predict. We compiled sequences of 346 aberrant 5′splice sites (5′ss) that were activated by mutations in 166 human disease genes. Mutations within the 5′ss consensus accounted for 254 cryptic 5′ss and mutations elsewhere activated 92 de novo 5′ss. Point mutations leading to cryptic 5′ss activation were most common in the first intron nucleotide, followed by the fifth nucleotide. Substitutions at position +5 were exclusively G>A transitions, which was largely attributable to high mutability rates of C/G>T/A. However, the frequency of point mutations at position +5 was significantly higher than that observed in the Human Gene Mutation Database, suggesting that alterations of this position are particularly prone to aberrant splicing, possibly due to a requirement for sequential interactions with U1 and U6 snRNAs. Cryptic 5′ss were best predicted by computational algorithms that accommodate nucleotide dependencies and not by weight-matrix models. Discrimination of intronic 5′ss from their authentic counterparts was less effective than for exonic sites, as the former were intrinsically stronger than the latter. Computational prediction of exonic de novo 5′ss was poor, suggesting that their activation critically depends on exonic splicing enhancers or silencers. The authentic counterparts of aberrant 5′ss were significantly weaker than the average human 5′ss. The development of an online database of aberrant 5′ss will be useful for studying basic mechanisms of splice-site selection, identifying splicing mutations and optimizing splice-site prediction algorithms.
Biodiesel Production from Chlorella protothecoides Oil by Microwave-Assisted Transesterification

In this study, biodiesel production from microalgal oil by microwave-assisted transesterification was carried out to investigate its efficiency. Transesterification reactions were performed by using Chlorella protothecoides oil as feedstock, methanol, and potassium hydroxide as the catalyst. Methanol:oil ratio, reaction time and catalyst:oil ratio were investigated as process parameters affected methyl ester yield. 9:1 methanol/oil molar ratio, 1.5% KOH catalyst/oil ratio and 10 min were optimum values for the highest fatty acid methyl ester yield.
Matrix metalloproteinase (MMP-9 and MMP-2) gene polymorphisms influence allograft survival in renal transplant recipients.

BACKGROUND Matrix metalloproteinases (MMPs), especially basement membrane-degrading MMP-9 and MMP-2, play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in MMP-9 (836A>G, 1721G>C and 2003G>A) and MMP-2 (-735C>T) genes with risk of allograft rejection in renal transplant recipients of North India. METHODS Three hundred and six renal transplant recipients categorized into 228 non-rejecters and 78 rejecters were genotyped for MMP-9 and MMP-2 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS A significant difference in genotype/allele frequencies was observed between healthy individuals in comparison to non-rejecters/rejecters for MMP-9 836A>G, MMP-9 2003G>A and MMP-2 -735C>T. Mutant allele carriers for MMP-9 2003G>A [GA+AA-; odds ratio (OR) = 0.45, 95% confidence intervals (95% CI) = 0.24-0.85, P = 0.014] and MMP-2 -735C>T (CT+TT-; OR = 0.40, 95% CI = 0.18-0.91, P = 0.029) demonstrated significantly reduced risk for allograft rejection. The mean time to first rejection episode was significantly higher in GA/AA and CT/TT genotype recipients for MMP-9 2003G>A (log P = 0.026) and MMP-2 -735C>T (log P = 0.003), respectively. Haplotypes with mutant alleles for MMP-9 1721C>G-2003G>A and mutant allele genotype combinations for both MMP-9 2003G>A and MMP-2 -735C>T conferred significantly reduced risk for allograft rejection. CONCLUSION Mutant alleles for MMP-9 2003G>A and MMP-2 -735C>T are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.
A Multicenter, Open Labeled, Randomized, Phase III Study Comparing Lopinavir/Ritonavir Plus Atazanavir to Lopinavir/Ritonavir Plus Zidovudine and Lamivudine in Naive HIV-1-Infected Patients: 48-Week Analysis of the LORAN Trial

Objective: The primary aim of the study was to compare the metabolic side effects of a nucleoside analogue-containing regimen with a nucleoside analogue-sparing double protease inhibitor regimen. A secondary goal was to test for efficacy of a double-PI regimen. Design: Multicenter, randomized, open-label, phase III clinical trial. Subjects: Adult HIV-1-infected individuals naïve to antiretroviral therapy with viral load above 400 HIV-RNA copies/ml were randomized (1:1) to either 400 mg lopinavir /100 mg ritonavir (LPV/r) BID plus 150 mg lamivudine/300 mg zidovudine (CBV) BID versus LPV/r BID plus 300 mg atazanavir (ATV) QD. Main outcome measure was the virologic failure in both groups, defined as viral load ≥50 copies/ml at week 48. Results: In the CBV/LPV/r-arm, 29 out of 35 patients [(83%; 95% confidence interval (CI) 66.9-92.2%] and 18 out of 40 patients (45%; 95% CI 29.7-61.5%) in the ATV/LPV/r-arm had a HIV-RNA level <50 copies/ml at week 48. The intent-to-treat analysis revealed inferior virologic response in the ATV/LPV/r arm (Chi-Q and Fisher´s Exact Test p<0.001) and resulted in premature termination of the trial. Eleven patients in the ATV/LPV/r-arm discontinued therapy because of virological failure. These failures mostly presented with low level replication (<1,000 copies/ml). Increases in CD4 cell counts was significantly more rapid in the ATV/LPV/r arm (p=0.02), but comparable at week 48. Conclusions: ATV/LPV/r had less virologic efficacy than the conventional RTI-based regimen and resulted in a high virological failure rate with low level replication.
Bayesian Real-Time Dynamic Programming

Real-time dynamic programming (RTDP) solves Markov decision processes (MDPs) when the initial state is restricted, by focusing dynamic programming on the envelope of states reachable from an initial state set. RTDP often provides performance guarantees without visiting the entire state space. Building on RTDP, recent work has sought to improve its efficiency through various optimizations, including maintaining upper and lower bounds to both govern trial termination and prioritize state exploration. In this work, we take a Bayesian perspective on these upper and lower bounds and use a value of perfect information (VPI) analysis to govern trial termination and exploration in a novel algorithm we call VPI-RTDP. VPI-RTDP leads to an improvement over state-of-the-art RTDP methods, empirically yielding up to a three-fold reduction in the amount of time and number of visited states required to achieve comparable policy performance.
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes

Chd1 (Chromodomain Helicase DNA Binding Protein 1) is a conserved ATP-dependent chromatin remodeler that maintains the nucleosomal structure of chromatin, but the determinants of its specificity and its impact on gene expression are not well defined. To identify the determinants of Chd1 binding specificity in the yeast genome, we investigated Chd1 occupancy in mutants of several candidate factors. We found that several components of the PAF1 transcription elongation complex contribute to Chd1 recruitment to highly transcribed genes and identified Spt4 as a factor that appears to negatively modulate Chd1 binding to chromatin. We discovered that CHD1 loss alters H3K4me3 and H3K36me3 patterns throughout the yeast genome. Interestingly, the aberrant histone H3 methylation patterns were predominantly observed within 1 kb from the transcription start site, where both histone H3 methylation marks co-occur. A reciprocal change between the two marks was obvious in the absence of Chd1, suggesting a role for CHD1 in establishing or maintaining the boundaries of these largely mutually exclusive histone marks. Strikingly, intron-containing genes were most susceptible to CHD1 loss and exhibited a high degree of histone H3 methylation changes. Intron retention was significantly lower in the absence of CHD1, suggesting that CHD1 function as a chromatin remodeler could indirectly affect RNA splicing.