Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites

Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Examination of isoniazid metabolites revealed that rapid acetylators hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.
Reassessment of inclusion body-based production as a versatile opportunity for difficult-to-express recombinant proteins

Abstract The production of recombinant proteins in the microbial host Escherichia coli often results in the formation of cytoplasmic protein inclusion bodies (IBs). Proteins forming IBs are often branded as difficult-to-express, neglecting that IBs can be an opportunity for their production. IBs are resistant to proteolytic degradation and contain up to 90% pure recombinant protein, which does not interfere with the host metabolism. This is especially advantageous for host-toxic proteins like antimicrobial peptides (AMPs). IBs can be easily isolated by cell disruption followed by filtration and/or centrifugation, but conventional techniques for the recovery of soluble proteins from IBs are laborious. New approaches therefore simplify protein recovery by optimizing the production process conditions, and often include mild resolubilization methods that either increase the yield after refolding or avoid the necessity of refolding all together. For the AMP production, the IB-based approach is ideal, because these peptides often have simple structures and are easy to refold. The intentional IB production of almost every protein can be achieved by fusing recombinant proteins to pull-down tags. This review discusses the techniques available for IB-based protein production before considering technical approaches for the isolation of IBs from E. coli lysates followed by efficient protein resolubilization which ideally omits further refolding. The techniques are evaluated in terms of their suitability for the process-scale production and downstream processing of recombinant proteins and are discussed for AMP production as an example.
Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment

Background. Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method.
Life satisfaction and its relationship with spiritual well-being and religious practice in Iranian adolescent girls

Abstract Introduction During recent years, special attention has been given to spiritual well-being and religious practice in the field of health. This study aimed to determine the predictors of life satisfaction among adolescent girls in Tabriz, Iran, 2015. Materials and methods This cross-sectional study was conducted on 520 female students studying in high schools who were selected using the cluster sampling method. Data collection was carried out through the questionnaires of socio-demographic characteristics, spiritual well-being (SWBS), religious practice (Arcury and colleagues) and life satisfaction (SWLS). Multivariate linear regression model was used for data analysis. Results The mean score of life satisfaction was 22.0 (SD: 6.0) from the attainable score of 5–35. The mean score (SD) of spiritual well-being was 90.2 (16.2), ranging from 20 to 120. The mean score of the religious practice was 32.1 (10.5) out of the achievable score range of 0–60. Multivariate linear regression analysis showed that existential well-being and sufficiency of income for expenses were predictors of life satisfaction and they explained 41.8% of the variance in the life satisfaction score. Conclusion The findings of the present study confirm the importance of existential well-being and a modifiable variable (sufficiency of income) in the life satisfaction. Thus, it is necessary to provide strategies to promote spirituality and improve the income status for improving adolescents’ life satisfaction.
Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Small cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G‐banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M‐FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M‐FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes. © 2002 Wiley‐Liss, Inc.
Surface‐enhanced laser desorption/ionization time of flight mass spectrometry protein profiling identifies ubiquitin and ferritin light chain as prognostic biomarkers in node‐negative breast cancer tumors

Novel prognostic biomarkers are imperatively needed to help direct treatment decisions by typing subgroups of node‐negative breast cancer patients. The current study has used a proteomic approach of SELDI‐TOF‐MS screening to identify differentially cytosolic expressed proteins with a prognostic impact in 30 node‐negative breast cancer patients with no relapse versus 30 patients with metastatic relapse. The data analysis took into account 73 peaks, among which 2 proved, by means of univariate Cox regression, to have a good cumulative prognostic‐informative power. Repeated random sampling (n = 500) was performed to ensure the reliability of the peaks. Optimized thresholds were then computed to use both peaks as risk factors and, adding them to the St. Gallen ones, improve the prognostic classification of node‐negative breast cancer patients. Identification of ubiquitin and ferritin light chain (FLC), corresponding to the two peaks of interest, was obtained using ProteinChip LDI‐Qq‐TOF‐MS. Differential expression of the two proteins was further confirmed by Western blotting analyses and immunohistochemistry. SELDI‐TOF‐MS protein profiling clearly showed that a high level of cytosolic ubiquitin and/or a low level of FLC were associated with a good prognosis in breast cancer.
Species limits in avian malaria parasites (Haemosporida): how to move forward in the molecular era

SUMMARY Delimiting species of malaria parasites (Haemosporida) has become increasingly problematic as new lineages of parasites are identified solely by molecular information, particularly mitochondrial cytochrome b sequence data. In this review, we highlight some of the issues, both historical and contemporary, that have hindered the development of objective criteria to diagnose, delimit and define species of haemosporidians. Defining species is not the focal interest of most researchers, most of whom merely wish to determine whether lineages identified in their samples match those of other researchers, and if so, where and in which host species. Rather than revisiting all the issues with respect to delimiting and naming species, we instead focus on finding a practical near-term resolution to the ‘species problem’ that utilizes the community's largest resource: mitochondrial cytochrome b DNA sequences. We recommend a standardized procedure to ‘tag’ these sequences, based on per cent sequence similarity, that will allow researchers to directly assess the novelty, known hosts and geographic distribution of avian malaria parasite lineages.
The Expansion of Real Estate

The definition of commercial real estate for institutional investment purposes is undergoing a change in two ways. First, real estate is increasingly being absorbed upward into more broadly defined asset buckets, such as real assets or private markets, in which the distinction between real estate and the other asset types is becoming increasingly fuzzy. Second, the asset class is expanding downward to include more specialty property types that were previously not considered suitable for institutional investors. In this article, the authors discuss these trends and their causes and consequences and relate them to the other articles contained in this special real estate issue.
Automatic diagnosing of infant hip based on Graf criteria

In this paper, we proposed an automatic diagnosis method in detection of infants hips, and experimental results on real ultrasonic images have shown its fastness and capability in the eld. Four procedures, pre-processing of raw images, segmenting, feature extracting and diagnosing, are included in proposed method. Pre-processing mainly focus on obtaining interested region from raw images. Segmenting, followed by features extracting from segmented images, proceeded at once after pre-processing. The algorithm of segmentation we used here is region-scalable tting energy model. Finally, we obtain two most important reference indexes of Graf criteria, angles α and β, by tting lines with least squares method applied. Accordingly, hips are classi ed into one of four types, including maturity, dysplasia, severe dysplasia and dislocation, according to aforementioned indexes. Accuracy on practical images reaches 80.4% with 93 images tested.
An exploratory study of reiki experiences in women who have cancer.

AIMS To explore the perceptions and experiences of reiki for women who have cancer and identify outcome measures for an intervention study. METHODS A cross-sectional qualitative study of 10 women who had received reiki after cancer treatment was conducted. Interviews were audiotaped, transcribed and coded using framework analysis. RESULTS Key themes identified were: limited understanding of reiki prior to receiving any reiki; release of emotional strain during reiki-feelings of a release of energy, a clearing of the mind from cancer, inner peace/relaxation, hope, a sense of being cared for; experience of physical sensations during reiki, such as pain relief and tingling; physical, emotional and cognitive improvements after reiki, such as improved sleep, a sense of calm and peace, reduced depression and improved self-confidence. CONCLUSION Findings suggest that reiki could be a beneficial tool in the self-management of quality of life issues for women who have cancer.
Self-Deceptive Enhancement and Family Environment: Possible Protective Factors Against Internalization of the Thin Ideal

We examined the degree to which self-deceptive enhancement and/or family environment moderated the relationship between awareness and internalization of sociocultural appearance standards. We administered the Sociocultural Attitudes Towards Appearance Questionnaire, the Family Environment Scale, the Family History of Eating questionnaire, and the Balanced Inventory of Desirable Responding to female undergraduate students (N = 232) and tested our predictions with moderator regression. Self-deceptive enhancement appeared to moderate the relationship between awareness and internalization. Family history of weight and appearance preoccupation also marginally moderated the relationship whereas general family environment did not. High levels of self-deceptive enhancement may serve as a protective factor against internalization of sociocultural pressures. High levels of family preoccupation with weight and appearance may have the opposite effect, making women more vulnerable to internalization. Portions of this paper were presented at the 2002 conference of the Association for Advancement of Behavior Therapy.
Structural Characterization of the Loop at the Alpha-Subunit C-Terminus of the Mixed Lineage Leukemia Protein Activating Protease Taspase1

Type 2 asparaginases, a subfamily of N-terminal nucleophile (Ntn) hydrolases, are activated by limited proteolysis. This activation yields a heterodimer and a loop region at the C-terminus of the α-subunit is released. Since this region is unresolved in all type 2 asparaginase crystal structures but is close to the active site residues, we explored this loop region in six members of the type 2 asparaginase family using homology modeling. As the loop model for the childhood cancer-relevant protease Taspase1 differed from the other members, Taspase1 activation as well as the conformation and dynamics of the 56 amino acids loop were investigated by CD and NMR spectroscopy. We propose a helix-turn-helix motif, which can be exploited as novel anticancer target to inhibit Taspase1 proteolytic activity.
Compliance, persistence, and preference outcomes of postmenopausal osteoporotic women receiving a flexible or fixed regimen of daily risedronate: A multicenter, prospective, parallel group study.

OBJECTIVE The aim of this study was to examine the level of compliance and persistence in patients with postmenopausal osteoporosis (OP) receiving daily risedronate (5 mg) with either fixed dosing of three different timing regimens (A: before breakfast; B: in-between meals; C: before bedtime) or with flexible dosing and the effect on urinary N-terminal telopeptide of Type 1 collagen (NTX-1). METHODS The study included 448 patients with postmenopausal OP. Patients were randomly assigned into six treatment groups each with a permutation of the treatment sequence (ABC, BCA, etc.) in the crossover phase (3 x 1 week) and randomized to 23 weeks of either the daily flexible (either regimen A, B or C) or fixed timing (only regimen A, B, or C) in the patient's preference phase. Urinary NTX-1 was tested. RESULTS A total of 433 patients participated in the patient's preference phase (49.7% preferred flexible and 50.3% fixed timing). There was no significant difference between the proportion of responders who were both compliant and persistent in the flexible (54.4%) and fixed regimens (53.7%) (p=0.8803). A significant difference between the flexible and fixed regimens was seen in persistence in favor of the flexible regimen (p=0.0306). There was no significant difference between the flexible and fixed regimens in terms of compliance (p=0.4611). Change in urinary NTX-1 did not show any difference between the two regimens. At the final visit, 51% of patients in the flexible and 55% in the fixed regimen group considered the used risedronate regimen as excellent or very good (p=0.1440). CONCLUSION A flexible dosing with daily risedronate appears be a valuable option in terms of compliance and persistence for patients with postmenopausal OP.
Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody

Diafiltration of a protein solution into a new buffer is a common final step in biopharmaceutical manufacturing. However, the excipient concentrations in the retentate are not always equal to their corresponding concentrations in the new buffer (diafiltration buffer). This phenomenon was observed repeatedly during diafiltration of different therapeutic monoclonal antibodies in which the concentrations of histidine and either sorbitol or sucrose (depending on which was chosen for the diafiltration buffer) in the retentate were lower than in the diafiltration buffer. Experimental studies and theoretical analyses of the ultrafiltration/diafiltration (UF/DF) step were carried out to determine the primary causes of the phenomenon and to develop a mathematical model capable of predicting retentate excipient concentrations. The analyses showed that retentate histidine concentration was low primarily because of repulsive charge interactions between positively‐charged histidine molecules and positively‐charged protein molecules, and that volume exclusion effects were secondary for like‐charged molecules. The positively‐charged protein molecules generate an electrical potential that cause an uneven distribution of charged histidine molecules. This interaction was used to construct a mathematical model based on the Poisson‐Boltzmann equation. The model successfully predicted the final histidine concentration in the diafiltered product (retentate) from the UF/DF development and production runs, with good agreement across a wide range of protein and histidine concentrations for four therapeutic monoclonal antibodies. The concentrations of uncharged excipients (sorbitol or sucrose) were also successfully predicted using previously established models, with volume exclusion identified as the primary cause of differences in uncharged excipient concentrations in the retentate and diafiltration buffer. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. , 2009
Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract.

BACKGROUND AND OBJECTIVES Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of ESRD in children, but the proportion of patients with individual CAKUT entities progressing to ESRD during adulthood and their long-term clinical outcomes are unknown. This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients with CAKUT were compared with age-matched patients who were undergoing RRT for other renal disorders on the basis of data from the European Renal Association-European Dialysis and Transplant Association Registry. Competing risk and Cox regression analyses were conducted. RESULTS Of 212,930 patients commencing RRT from 1990 to 2009, 4765 (2.2%) had renal diagnoses consistent with CAKUT. The proportion of incident RRT patients with CAKUT decreased from infancy to childhood and then increased until age 15-19 years, followed by a gradual decline throughout adulthood. Median age at RRT start was 31 years in the CAKUT cohort and 61 years in the non-CAKUT cohort (P<0.001). RRT was started earlier (median, 16 years) in patients with isolated renal dysplasia than in those with renal hypoplasia and associated urinary tract disorders (median, 29.5-39.5 years). Patients with CAKUT survived longer than age- and sex-matched non-CAKUT controls because of lower cardiovascular mortality (10-year survival rate, 76.4% versus 70.7%; P<0.001). CONCLUSIONS CAKUT leads to ESRD more often at adult than pediatric age. Treatment outcomes differ from those of acquired kidney diseases and vary within CAKUT subcategories.
A rapid two-dimensional data collection system for the study of ferroelectric materials under external applied electric fields

The diffraction response of the PMN–PT relaxor piezoelectric 67% Pb(Mg1/3Nb2/3)O3–33% PbTiO3 has been recorded as a function of externally applied electric field. The DC field was applied using a specially designed sample cell for in situ single-crystal diffraction experiments. The coverage of a significantly large section of reciprocal space allowed precise phase analysis.
From strategic goals to business model innovation paths: an exploratory study

Purpose The purpose of this paper is to analyse how different strategic goals of (micro-, small- and medium-sized firms=SMEs) relate to the business model innovation (BMI) paths that SMEs take when improving their business. Design/methodology/approach The authors conducted 11 in-depth case studies involving SMEs innovating their business models (BMs). Findings The authors found evidence that strategic goals of SMEs (start new business, growth and profitability) lead them to alternative innovation path in terms of BM components affected. Growth seekers start from the right-hand side of a BM Canvas, while profitability seekers start from the back end, the left side of a Canvas; and new businesses adopt a cyclical approach considering BM components in turn, while at the same time redesigning and testing the BM. The findings of this study also indicate that all three paths gradually lead to improvement in several BM components. Research limitations/implications Findings indicate that a strategic management view in which strategic goals define BMI also applies to SMEs. The distinctive BMI paths that the authors identified provide evidence to suggest that, although the SMEs may not have an explicitly formulated strategy, their strategic goals determine the type of improvements they make to their BM. All three SME groups started their improvements from different BM components and changed several elements in their BMs in a specific order, forming distinctive BMI paths. Finally, to understand the BMI in SMEs better, more research is needed into BMI processes and into the way BMI is managed in SMEs. Practical implications The findings of this study help SMEs to anticipate the next steps in their path towards an improved BM. By mirroring their approach to the BMI paths, they can better manage their BM makeover process and focus on their innovation activities. For providers of BMI tools and methods, the study indicates which SME innovation tasks could be supported by tools and how the tools should be aligned with the BMI paths. Originality/value BMI is attracting growing attention in both research and practice. However, knowledge concerning BMI in SMEs is limited. The authors contributed to BMI research by focussing on the BMI paths of SMEs, i.e. the often sequential, non-linear and iterative steps taken to improve the business by making changes to specific BM components.