Miracle-dz/UniFAR-FTUs huggingface dataset:
Monitoring of minimal residual disease in patients with core binding factor acute myeloid leukemia and the impact of C-KIT, FLT3, and JAK2 mutations on clinical outcome

Mutational analysis of C-KIT, fms-like tyrosine kinase 3 (FLT3), and JAK2 genes was performed in 60 patients with core binding factor acute myeloid leukemia (CBF-AML). Patients reaching molecular remission had lower incidence of relapse and better overall survival (OS) than those not achieving molecular remission (p = 0.008 and 0.044, respectively). The overall incidence of C-KIT mutations was 33.3%, FLT3/internal tandem duplication (ITD) 6.6%, FLT3D835 10.0% and JAK2V617F mutations 3.3%. C-KIT mutations did not predict for clinical/molecular relapse (p = 0.33). OS of patients with C-KIT mutations was identical to patients without them when all patients with CBF-AML were analyzed together (p = 0.58). When AML1/ETO-positive patients were evaluated separately, OS in C-KIT-mutated patients was slightly inferior to unmutated ones (p = 0.14). Patients with CBF-AML with a mutated C-KIT gene were also more prone to extramedullary disease (p = 0.08). Of six patients harboring various FLT3D835 mutations, four (66.7%) relapsed, whereas among 43 cases without these mutations, 16 relapses (37%) were observed (p = 0.08). Our results on minimal residual disease, C-KIT, and FLT3/ITDs are in line with previous studies. Surprisingly, a possible role for FLT3D835 mutations was noted in addition. These results need validation in even larger patient cohorts than ours. For routine clinical practice, it may be meaningful to screen for C-KIT mutations in AML1/ETO-positive patients, as well as for FLT3D835 mutations in CBF-AML.
The effect of stopping smoking on perceived stress levels.

AIMS Many smokers believe that smoking helps them to cope with stress, and that stopping smoking would deprive them of an effective stress management tool. Changes in stress levels following long-term smoking cessation are not well mapped. This longitudinal project was designed to provide more robust data on post-cessation changes in perceived stress levels by following a cohort of smokers admitted to hospital after myocardial infarction (MI) or for coronary artery bypass (CAB) surgery, as such patients typically achieve higher continuous abstinence rates than other comparable samples. DESIGN A total of 469 smokers hospitalized after MI or CAB surgery and wanting to stop smoking were seen in the hospital and completed 1-year follow-ups. Ratings of helpfulness of smoking in managing stress at baseline, smoking status (validated by salivary cotinine concentration) and ratings of perceived stress at baseline and at 1-year follow-up were collected. FINDINGS Of the patients, 41% (n = 194) maintained abstinence for 1 year. Future abstainers and future smokers did not differ in baseline stress levels or in their perception of coping properties of smoking. However, abstainers recorded a significantly larger decrease in perceived stress than continuing smokers, and the result held when possible confounding factors were controlled for (P < 0.001). CONCLUSIONS In highly dependent smokers who report that smoking helps them cope with stress, smoking cessation is associated with lowering of stress. Whatever immediate effects smoking may have on perceived stress, overall it may generate or aggravate negative emotional states. The results provide reassurance to smokers worried that stopping smoking may deprive them of a valuable coping resource.
Frequent and long-term absence as a risk factor for work disability and job termination among employees in the private sector

Objectives: Frequent and long-term absentees were monitored over 5 years with regard to the risk of work disability and job termination. Methods: A prospective longitudinal cohort study in 53 990 employees of Dutch postal and telecommunications companies. In the first year of the study, employees who were absent four times or more (frequent absentees; n = 4126), for 6 weeks or more (long-term absentees; n = 3585), and combined frequent and long-term absentees (n = 979) were distinguished, together with a reference population consisting of 45 300 employees. The disability rate (defined as the number of employees who were absent for >1 year per 100 employee-years) and the risk of job termination were determined over a period of 4 years. Results: In the reference population, women had a higher disability rate (2.2 per 100 employee-years) than men (0.8 per 100 employee-years). Frequent absentees had a disability rate amounting to 2.5 per 100 employee-years in men and 4.2 per 100 employee-years in women. Long-term absentees had a disability rate of 6.7 per 100 employee-years in men and 9.1 per 100 employee-years in women. Combined frequent and long-term absentees had an even higher disability rate. The risk of employment being terminated (involuntarily) was higher in prior absentees as compared with the reference population (RR = 1.2–2.1 for job termination and RR = 1.5–2.5 for involuntary job termination). In men, absences due to neoplasms, mental disorders and respiratory disorders were associated with an increased disability risk as compared with musculoskeletal disorders. Neoplasms and mental disorders were also associated with a higher risk of job termination in men, whereas infectious and neurological diseases were associated with a higher risk of job termination in women. Conclusions: Prior frequent and/or long-term absentees show high work disability in a 4-year follow-up period. Moreover, they are at higher risk of (involuntary) job termination.
Serum ferritin in HIV-positive patients is related to immune deficiency and inflammatory activity

To analyse the prevalence of high ferritin levels in asymptomatic HIV patients and its related factors we conducted a cross-sectional study of a cohort of HIV outpatients in regular follow-up. Epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about cardiovascular risk factors and underwent a physical examination and a 12-h fasting blood analysis. High ferritin levels were defined as a plasma ferritin level >200 µg/L in women and >300 µg/L in men. A total of 571 patients (78.1% men) were included. Median age was 43.2 years, HIV sexual transmission 68.5%, median CD4 count 474 cells/µL, 36.3% AIDS cases, 86.2% on antiretroviral therapy and 74.8% of them with undetectable viral load; 14.6% metabolic syndrome criteria, and mean cardiovascular risk at 10 years 6.67%. High ferritin levels prevalence was 11%, and related factors were a CD4 count <350 cells/µL (odds ratio, OR 2.37 [1.3–4.1], p = 0.003), ultrasensitive C-reactive protein >3 mg/L (OR 2.67 [1.5–4.7], p = 0.001) and chronic hepatitis C virus infection (OR 2.77 [1.5–4.9], p = 0.001). High ferritin levels are not uncommon in HIV patients, and they correlate with immunosuppression defined as CD4 count <350 cells/µL, higher ultrasensitive C-reactive protein and hepatitis C virus infection, and in contrast to the general population, they are not related to increased cardiovascular risk or metabolic syndrome.
Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture

Abstract Growth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.
Common variants of HTR1A and SLC6A4 confer the increasing risk of Schizophrenia susceptibility: A population‐based association and epistasis analysis

Schizophrenia (SZ) is a complex psychiatric disorder strongly influenced by genetic variants, some of which are associated with mood disorders. The neurotransmitter 5‐hydoxytryptamine (5‐HT) and its related biochemical factors have been shown to play a significant role in maintaining mood balance. Recent studies evaluating the association between SZ and genetic polymorphisms in a serotonin transporter (encoded by SLC6A4) and serotonin receptor 1A (encoded by HTR1A) show conflicting results. In this study, we performed a case‐control association analysis using 4,000 individuals with Chinese‐Han ancestry. Of these participants, 1,000 were SZ cases and 3,000 were healthy controls. Thirty‐six single nucleotide polymorphisms (SNPs) located in SLC6A4 and HTR1A were genotyped in our 4,000 study samples. Of those, 33 polymorphic SNPs with a minor allele frequency >0.05 were used for further analysis. We found that rs878567 in HTR1A (asymptotic P‐value = 3.89×10−4, corrected P‐value = 0.0106) was significantly associated with SZ. Further haplotype‐based analyses revealed that a two‐SNP haplotype, rs2054847‐rs140701 (TG) in gene SLC6A4, was significantly associated with SZ (P‐value = 1.63×10−4 and corrected P‐value = 0.002799). We did not identify any significant epistatic interactions between the two genes. Our findings provide supportive evidence that genetic polymorphisms in SLC6A4 and HTR1A may influence the risk of SZ in Han Chinese individuals. © 2015 Wiley Periodicals, Inc.
The Polyphenols Stability, Enzyme Activity and Physico-Chemical Parameters During Producing Wild Elderberry Concentrated Juice

The influence of processing wild elderberry into concentrated juice on polyphenols (total phenols, flavonoids, non-flavonoids, anthocyanins, flavan-3-ols, hydrolysed tannins) stability, activity of polyphenol oxidase (PPO) and peroxidase (POD), and changes of physico-chemical parameters (total and soluble dry matter, total acidity, pH, sugars) were investigated. The amounts of total phenols, flavonoids, non-flavonoids, falvan-3-ols and hydrolysed tannins were analyzed using Folin-Ciocalteu colorimetric method, while the total anthocyanins were determined by bisulphite bleaching method. Total phenols ranged from 25.87 mg/g DM to 38.87 mg/g DM. Total anthocyanins were the most abundant polyphenols in all investigated samples (raw elderberries, elderberries after blanching, elderberry juice after disintegration and pressing, concentrated elderberry juice) and their concentration ranged from 13.12 mg/g DM to 25.67 mg/g DM. Other polyphenols determined in high concentration were hydrolysed tannins, followed by fl avan-3-ols, flavonoids and nonfavonoids. After blanching, the concentration of all polyphenols did not decrease significantly. After disintegration of elderberries the concentration of all polyphenols increased, probably due to inactivation of PPO and POD and better isolation of polyphenols from homogenized puree. During processing of elderberry juice into concentrated juice most polyphenols were stable. Total acidity and pH value were not changed during processing, whereas the amounts of total and reducing sugar increased after pressing and additionally after concentration. The obtained results suggest that raw elderberries as well as elderberry concentrated juice are high potential source of polyphenols especially anthocyanins.
Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations

NMR spectroscopic studies are undertaken with derivatives of 2‐pyrazinecarboxylic acid. Complete and unambiguous assignment of chemical shifts (1H, 13C, 15N) and coupling constants (1H,1H; 13C,1H; 15N,1H) is achieved by combined application of various 1D and 2D NMR spectroscopic techniques. Unequivocal mapping of 13C,1H spin coupling constants is accomplished by 2D (δ,J) long‐range INEPT spectra with selective excitation. Phenomena such as the tautomerism of 3‐hydroxy‐2‐pyrazinecarboxylic acid are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Further Understanding the Systemic Effects of Childhood Sexual Abuse: A Comparison of Two Groups of Clinical Couples

ABSTRACT This study addressed the impact of traumatic experiences on dyadic relationships by comparing general stress and trauma symptoms and relationship impairment measures between two clinical groups: female childhood sexual abuse (CSA) survivors (n = 15) and their male partners, and a control group of couples who reported no CSA (n = 17). Both female CSA survivors and their partners reported higher symptoms of stress, suggesting support for the theory of secondary traumatic stress. Relationship impairment results did not support the hypothesis that CSA would negatively impact the dyadic functioning of couples. Clinical implications and recommendations for future research are provided.
Exergy Analysis of an Absorption Refrigeration System Using an Iconic Liquid as a Working Fluid in the Chemical Compressor

The first and second law of thermodynamics are applied to an ionic-liquid (IL) based absorption refrigeration system for high power electronics cooling. The IL is a salt in a liquid state usually with an organic cation and inorganic anion. It provides an alternative to the normally toxic working fluids used in the chemical compression loop, such as ammonia in conventional absorption systems. The use of ILs also eliminates crystallization and metal-compatibility problems of the water/LiBr system. In this study, mixtures of refrigerants and imidazolium-based ILs are theoretically explored as the working fluid pairs in a miniature absorption refrigeration system, so as to utilize waste-heat to power a refrigeration/heat pump system for electronics cooling. A mathematical model based on exergy analysis is employed to characterize the performance for specific refrigerant/IL pairs. Both the coefficient of performance (COP) and the exergetic coefficient of performance (ECOP) of the absorption system and components are evaluated. The thermodynamic properties of ILs are evaluated using the correlations based on group contribution methods. A non-random two-liquid (NRTL) model is built and used to predict the solubility of the mixtures. The properties of the refrigerants are determined using REFPROP 6.0 software. Saturation temperatures at the evaporator and condenser are set at 25 o C and 50 o C, respectively. The power dissipation at the evaporator is fixed at 100 W with the operating temperature set at 85 o C, which are the benchmark conditions for high performance microprocessor chip cooling. The desorber and absorber outlet temperatures are adjusted to evaluate the system performance variation with respect to the operating condition change. The effect of the refrigerant/IL compatibility, alkyl chain length of the IL cation, and thermodynamic properties of the refrigerants, such as latent heat of evaporation, on the ECOP is investigated. Also the exergy destruction of each component of the cycle is evaluated and discussed as a means to identify the critical component(s) of the system that would require optimization.
Effect of tibial plateau leveling osteotomy on femorotibial contact mechanics and stifle kinematics.

OBJECTIVE To evaluate the effects of tibial plateau leveling osteotomy (TPLO) on femorotibial contact mechanics and 3-dimensional (3D) kinematics in cranial cruciate ligament (CrCL)-deficient stifles of dogs. STUDY DESIGN In vitro biomechanical study. ANIMALS Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. METHODS Digital pressure sensors placed subjacent to the menisci were used to measure femorotibial contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135 degrees. Three-dimensional static poses of the stifle were obtained using a Microscribe digitizing arm. Each specimen was tested under normal, CrCL-deficient, and TPLO-treated conditions. Repeated measures analysis of variance with a Tukey post hoc test (P<.05) was used for statistical comparison. RESULTS Significant disturbances to all measured contact mechanical variables were evident after CrCL transection, which corresponded to marked cranial tibial subluxation and increased internal tibial rotation in the CrCL-deficient stifle. No significant differences in 3D femorotibial alignment were observed between normal and TPLO-treated stifles; however, femorotibial contact area remained significantly smaller and peak contact pressures in both medial and lateral stifle compartments were positioned more caudally on the tibial plateau, when compared with normal. CONCLUSION Whereas TPLO eliminates craniocaudal stifle instability during simulated weight bearing, the procedure fails to concurrently restore femorotibial contact mechanics to normal. CLINICAL RELEVANCE Progression of stifle osteoarthritis in dogs treated with TPLO may be partly the result of abnormal stifle contact mechanics induced by altering the orientation of the proximal tibial articulating surface.
GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice

Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca2+ and cGMP. Ca2+ regulates the activity of guanylate cyclase (GC) and the synthesis of cGMP by acting on a GC‐activating protein (GCAP). While this action is critical for rapid termination of the light response, the GCAP responsible has not been identified. To test if GCAP1, one of two GCAPs present in mouse rods, supports the generation of normal flash responses, transgenic mice were generated that express only GCAP1 under the control of the endogenous promoter. Paired flash responses revealed a correlation between the degree of recovery of the rod a‐wave and expression levels of GCAP1. In single cell recordings, the majority of the rods generated flash responses that were indistinguishable from wild type. These results demonstrate that GCAP1 at near normal levels supports the generation of wild‐type flash responses in the absence of GCAP2.
Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL).

INTRODUCTION Sequential high dose (SHiDo) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. METHODS To confirm this result in a multicenter trial, we randomized patients with aggressive NHL, to receive either eight cycles of CHOP or SHiDo. The primary endpoint was overall survival. RESULTS 129 evaluable patients were randomized to receive either CHOP or SHiDo: median age, 48 years; 62% male; stage III+IV: 73%; age adjusted International Prognostic Index 1/2/3: 21%/52%/27%. Toxicity grades 3+4 were more pronounced in the SHiDo-arm with 13% versus 3% of patients with fever; 34% versus 13% with infections; 13% versus 2% with esophagitis/dysphagia/gastric ulcer. The remission rates were similar in SHiDo and CHOP arms with 34%/37% complete remissions and 31%/31% partial remissions, respectively. After a median observation time of 48 months, there was no difference in overall survival at 3 years, with 46% for SHiDo and 53% for CHOP (P = 0.48). CONCLUSION In this multicenter trial, early intensification with SHiDo did not confer any survival benefit in previously untreated patients with aggressive NHL and was associated with a higher incidence of grades 3/4 toxicity.
Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada

Abstract Objective: The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC. Methods: A cost-utility analysis (CUA) was conducted using a three health state Markov model (‘event-free’, ‘relapsed’, and ‘dead’). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored. Results: Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230–$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA). Conclusion: Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.
Lizards as vectors of human salmonellosis

SUMMARY Human infections with Salmonella saintpaul have become more frequent in New Zealand in recent years. Most cases now occur in Otago. It is shown that wild lizards in Otago, particularly the common skink (Leiolopisma zelandica), carry S. saintpaul and that most if not all human outbreaks of this salmonella serotype are associated with either lizards or lizard infested areas. So far as is known this is the first report incriminating lizards as the probable cause of human salmonellosis.