Miracle-dz/UniFAR-FTUs huggingface dataset:
The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients

Cancer patients in developing and low‐income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14‐month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0–5 months, 6–12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6–12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6–12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib.
Effects of egg-adaptation on receptor-binding and antigenic properties of recent influenza A (H3N2) vaccine viruses

Influenza A virus (subtype H3N2) causes seasonal human influenza and is included as a component of influenza vaccines. The majority of vaccine viruses are isolated and propagated in eggs, which commonly results in amino acid substitutions in the haemagglutinin (HA) glycoprotein. These substitutions can affect virus receptor-binding and alter virus antigenicity, thereby, obfuscating the choice of egg-propagated viruses for development into candidate vaccine viruses. To evaluate the effects of egg-adaptive substitutions seen in H3N2 vaccine viruses on sialic acid receptor-binding, we carried out quantitative measurement of virus receptor-binding using surface biolayer interferometry with haemagglutination inhibition (HI) assays to correlate changes in receptor avidity with antigenic properties. Included in these studies was a panel of H3N2 viruses generated by reverse genetics containing substitutions seen in recent egg-propagated vaccine viruses and corresponding cell culture-propagated wild-type viruses. These assays provide a quantitative approach to investigating the importance of individual amino acid substitutions in influenza receptor-binding. Results show that viruses with egg-adaptive HA substitutions R156Q, S219Y, and I226N, have increased binding avidity to α2,3-linked receptor-analogues and decreased binding avidity to α2,6-linked receptor-analogues. No measurable binding was detected for the viruses with amino acid substitution combination 156Q+219Y and receptor-binding increased in viruses where egg-adaptation mutations were introduced into cell culture-propagated virus. Substitutions at positions 156 and 190 appeared to be primarily responsible for low reactivity in HI assays with post-infection ferret antisera raised against 2012–2013 season H3N2 viruses. Egg-adaptive substitutions at position 186 caused substantial differences in binding avidity with an insignificant effect on antigenicity.
Negative association between smoking and anti-saccharomyces cerevisiae antibodies in Crohn's disease.

BACKGROUND Crohn's disease (CD) is a polygenic multifactorial heterogeneous disease. Anti-Saccharomyces Cerevisiae antibodies (ASCA) correlate highly with CD and are present in 50-80% of patients. The reason for ASCA positivity or negativity in CD is unknown. The aim of our work was to analyse clinical, epidemiological and genetic characteristics in ASCA+ or ASCA- CD patients. METHODS 113 patients with CD were tested for ASCA (IgA and IgG) by using a commercial kit (Medipan Diagnostica). Age, gender, systemic manifestations, familial form of disease, age at diagnosis, location and behaviour of the disease, smoking habit as well as genotyping for -308 TNF gene polymorphisms were determined. RESULTS 38.9% CD patients were negative for both IgA and IgG ASCA while 61.1% were ASCA positive (respectively IgA and IgG: 31.9%; IgA only: 9.7%; IgG only: 19.5%). The only significant difference between ASCA+ and ASCA- patients was for smoking habit: there were 29% smokers in ASCA+ versus 50% in ASCA- CD patients (P = 0.03). This low proportion of smokers was more prominent in ASCA IgA+ patients than in isolated ASCA IgG+ patients (25.6% versus 45.5%) and was minimal in patients with high titers of ASCA IgA (0/8). Logistic regression showed smoking habit still borderline for significance (P = 0.057). CONCLUSIONS Our results suggest a negative association between smoking and ASCA positivity in CD. This association was more prominent for ASCA IgA+. It indicates that smoking habit should be taken into account when analysing ASCA status in CD patients and may suggest an influence of smoking on immunization against intestinal material.
Use of Performance-Enhancing Substances

Performance-enhancing substances (PESs) are used commonly by children and adolescents in attempts to improve athletic performance. More recent data reveal that these same substances often are used for appearance-related reasons as well. PESs include both legal over-the-counter dietary supplements and illicit pharmacologic agents. This report reviews the current epidemiology of PES use in the pediatric population, as well as information on those PESs in most common use. Concerns regarding use of legal PESs include high rates of product contamination, correlation with future use of anabolic androgenic steroids, and adverse effects on the focus and experience of youth sports participation. The physical maturation and endogenous hormone production that occur in adolescence are associated with large improvements in strength and athletic performance. For most young athletes, PES use does not produce significant gains over those seen with the onset of puberty and adherence to an appropriate nutrition and training program.
WNT7A Regulates Tumor Growth and Progression in Ovarian Cancer through the WNT/β-Catenin Pathway

Abnormal activation the WNT/β-catenin signaling pathway has been associated with ovarian carcinomas, but a specific WNT ligand and pertinent downstream mechanisms are not fully understood. In this study, we found abundant WNT7A in the epithelium of serous ovarian carcinomas, but not detected in borderline and benign tumors, normal ovary, or endometrioid carcinomas. To characterize the role of WNT7A in ovarian tumor growth and progression, nude mice were injected either intraperitoneally or subcutaneously with WNT7A knocked down SKOV3.ip1 and overexpressed SKOV3 cells. In the intraperitoneal group, mice receiving SKOV3.ip1 cells with reduced WNT7A expression developed significantly fewer tumor lesions. Gross and histologic examination revealed greatly reduced invasion of WNT7A knockdown cells into intestinal mesentery and serosa compared with the control cells. Tumor growth was regulated by loss or overexpression of WNT7A in mice receiving subcutaneous injection as well. In vitro analysis of cell function revealed that cell proliferation, adhesion, and invasion were regulated by WNT7A. The activity of the T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter was stimulated by overexpression of WNT7A in ovarian cancer cells. Cotransfection with WNT7A and FZD5 receptor further increased activity, and this effect was inhibited by cotransfection with SFRP2 or dominant negative TCF4. Overexpression of WNT7A stimulated matrix metalloproteinase 7 (MMP7) promoter, and mutation of TCF-binding sites in MMP7 promoter confirmed that activation of MMP7 promoter by WNT7A was mediated by β-catenin/TCF signaling. Collectively, these results suggest that reexpression of WNT7A during malignant transformation of ovarian epithelial cells plays a critical role in ovarian cancer progression mediated by WNT/β-catenin signaling pathway. Mol Cancer Res; 10(3); 469–82. ©2012 AACR.
Discrepancy of van der Corput sequences generated by piecewise linear transformations

Discrepancy of van der Corput sequences constructed by piecewise linear transformations with same slope β > 1 is discussed. If there is no eigenvalues of the Perron-Frobenius operator associated with the dynamical system in |z| > 1/β except 1, the discrepancy equals (logN) k+1/N, where k is the number of the non-Markov endpoints.
Mutational analysis of CACNA1G in idiopathic generalized epilepsy

Recent studies have strongly implicated low voltage‐activated/T‐type calcium channels (T‐channels) in the etiology of epilepsy. Here, we report the results of a mutational analysis of the CACNA1G gene, encoding the T‐channel CaV3.1/1G subunit, using a cohort of 123 mostly Japanese and Hispanic patients with idiopathic generalized epilepsies (IGE) and 360 healthy control individuals. We found 13 variants, including five which involved amino acid substitutions. One variant, c.1709C>T (Ala570Val), is present in a sporadic case of juvenile myoclonic epilepsy (JME) with early childhood absence and astatic seizures, but was not found in control samples. Another variant, c.3265G>T (Ala1089Ser), was observed in three family members affected with JME, and also in one control individual. Two JME patients and three control individuals harbored a third variant, c.2968G>A (Asp980Asn). Although not statistically significant, slightly faster inactivation decay rates were observed in some mutant channels. Our collective findings flag CACNA1G as a potential susceptibility locus for IGE subsyndromes that warrants closer investigation. © 2007 Wiley‐Liss, Inc.
Can fractional crystallization, mixing and assimilation processes be responsible for Jamaican-type adakites? Implications for generating Eoarchaean continental crust

Understanding how the Earth’s first continental land masses were generated is important because the processes responsible directly affected the evolution of the planet’s primordial silicate interior, and also its atmosphere and hydrosphere. Archaean continental crust is dominated by rocks of the trondhjemite–tonalite–granodiorite (TTG) suite. These can be divided into (1) a mid- to late Archaean (∼3·5–2·5 Ga) suite with low SiO2 and high MgO, Sr and transition element contents, and (2) an Eoarchaean (>3·5 Ga) suite with higher SiO2 and lower MgO, Sr and transition element concentrations. Cenozoic adakites are considered to be compositionally similar to mid- to late Archaean (∼3·5–2·5 Ga) TTGs, but not the oldest TTG rocks. Conversely, a suite of Early Eocene adakite-like rhyodacites (Jamaican-type adakites: JTA) from Jamaica are shown to be geochemically similar to the Eoarchaean TTGs. In contrast to newly discovered JTA-like rocks (Ryozen low Sr/Y) in Japan, new trace element and Nd–Hf radiogenic isotope data in this study confirm that the Jamaican JTA cannot be formed by complex mixing, assimilation and fractional crystallization processes. New partial melt models here explore several different source compositions (mid-ocean ridge basalt, ocean island basalt and oceanic plateau), mineral modes, melt modes and partition coefficients. The results of these models clearly demonstrate that the JTA and the Eoarchaean TTG can be generated by partial melting of plagioclase- and garnet-bearing amphibolite source regions with oceanic plateau-like compositions. Further modelling shows that the JTA and Eoarchaean TTG low MgO and transition element abundances can be derived from two dominant processes: (1) relatively shallow partial melting of subducting oceanic crust (compositionally similar to Mesozoic oceanic plateau basalt) whereby the slab melts ascend without interacting with a mantle wedge; (2) partial melting of oceanic plateau-like subducting oceanic crust followed by interaction of the slab melts with a thin and/or discontinuous (boudinage-like? ) mantle wedge whereby the expected increase of MgO, Ni, and Cr in the slab melts is obliterated by fractional crystallization of ferromagnesian minerals (mostly amphibole). Consequently, using the JTA as a modern analogue for Eoarchaean TTG production, we propose the existence of subduction zones consuming oceanic plateau-like oceanic crust in Eoarchaean times.
Double‐Blind Study of Gabapentin in the Treatment of Partial Seizures

Summary: Forty‐three patients completed a double‐blind, placebo‐controlled study of Gabapentin (GBP) as add‐on therapy in partial and secondarily generalized seizures. All patients were followed for an initial 3‐month baseline period, after which they were randomly allocated to receive either a placebo or 900 or 1,200 mg/day GBP for 3 months. A statistically significant difference in seizure frequency from the baseline to the treatment phase was noted between patients receiving placebo and GBP 1,200 mg, in whom seizure frequency decreased 57%. The GBP dosage of 900 mg appeared to be ineffective. A close relationship was observed between the serum GBP concentrations and the GBP dosage based on the seizure frequency. Serum GBP concentrations > 2 μg/ml resulted in a lower frequency of seizures. The adverse effects were minor and consisted mainly of transient drowsiness. GBP appears to be effective in the treatment of partial epileptic seizures in a dosage‐related manner
Temperature dependence of avalanche multiplication in submicron silicon devices

Photomultiplication initiated by both pure electron and pure hole injection has been measured in submicron Si p/sup +/-i-n/sup +/ and n/sup +/-i-p/sup +/ diodes with a variety of intrinsic region thicknesses and at temperatures between 15 and 420 K. A local analysis yields expressions for the ionization coefficients as functions of electric field and of temperature which obey Chynoweth's law. Multiplication at various temperatures is computed and compares favorably with experiment.
Role of Diffusion-Weighted Echo-Planar MR Imaging in Differentiation of Residual or Recurrent Head and Neck Tumors and Posttreatment Changes

BACKGROUND AND PURPOSE: The purpose of this work was to evaluate whether diffusion-weighted MR imaging can be used in differentiating residual or recurrent head and neck tumors from postoperative or postradiation changes. MATERIALS AND METHODS: This study included 32 patients clinically suspected for recurrent head and neck tumor after surgery (n=3), radiation therapy (n=13), or both (n=16). Diffusion-weighted MR imaging was done by using a single-shot spin-echo echo-planar sequence. The apparent diffusion coefficient (ADC) value of the suspected lesion was calculated and correlated with pathologic results. RESULTS: Adequate diffusion-weighted MR images and ADC maps were obtained in 30 patients (93.8%). The mean ADC value of residual or recurrent lesions (1.17 ± 0.33 × 10−3 mm2/s) was less than that of posttherapeutic changes (2.07 ± 0.25 × 10−3 mm2/s), and the difference was statistically significant (P < .001). When an ADC value of 1.30 × 10−3 mm2/s was used as a threshold value for differentiation, the best results were obtained with an accuracy of 87%, sensitivity of 84%, specificity of 90%, positive predictive value of 94%, and negative predictive value of 76%. CONCLUSIONS: Diffusion-weighted MR imaging with ADC measurement has promising results for differentiating residual or recurrent head and neck tumors from postoperative or postradiation changes.
Inter- and intrarater reliability of goniometry and hand held dynamometry for patients with subacromial impingement syndrome

The purpose of this study was to examine the intra- and interrater reliability of measuring shoulder range of motion (ROM) and strength among patients diagnosed with subacromial impingement syndrome (SAIS). Twenty-five patients (14 female patients; mean age, 60.4± 7.84 years) diagnosed with SAIS were assessed to determine the intrarater reliability for glenohumeral ROM. Twenty-five patients (16 female patients; mean age, 60.4± 7.80 years) and 76 asymptomatic volunteers (52 female volunteers; mean age, 29.4± 14.1 years) were assessed for interrater reliability. Dependent variables were active shoulder ROM and isometric strength. Intrarater reliability was fair-to-excellent for the SAIS patients (intraclass correlation coefficient [ICC], 0.52–0.97; standard error of measurement [SEM], 4.4°–9.9° N; coefficient of variation [CV], 7.1%–44.9%). Based on the ICC, 11 of 12 parameters (92%) displayed an excellent reliability (ICC> 0.75). The interrater reliability showed fair-to-excellent results (SAIS patients: ICC, 0.13–0.98; SEM, 2.3°–8.8°; CV, 3.6%–37.0%; controls: ICC, 0.11–0.96; SEM, 3.0°–35.4°; CV, 5.6%–26.4%). In accordance with the intrarater reliability, glenohumeral adduction ROM was the only parameter with an ICC below 0.75 for both samples. Painful shoulder ROM in the SAIS patients showed no influence on the quality of reliability for measurement. Therefore, these protocols should be considered reliable assessment techniques in the prevention, diagnosis, and treatment of painful shoulder conditions such as SAIS.
Resistance Steps and Asymmetric Conduction Induced by Currents in  ${\rm La}_{0.8}{\rm Ca}_{0.2}{\rm MnO}_{3}$ Films

A constant voltage mode of a power supply was adopted to study the current-induced effects in La0.8Ca0. 2MnO3 epitaxial thin films. After processed by a current of the density of ~3 × 105 A/cm2 for 1 minute, they exhibited anisotropic conduction. Like the behavior of p-n junctions, the current starts to increase dramatically in the forward direction at a threshold voltage (opening voltage Vop), e.g., ~2.3 V at 30 K. For a processing with extending duration, the resistance while processing dropped from 10 k¿ to 2 k¿. Current voltage curves measured following such a step showed more stable asymmetric characteristics and substantial reduction of Vop, which is ~0.8 V at 290 K and ~1.6 V at 50 K. Our results are useful for revealing the origin of asymmetric conduction induced by current and for potential application.
Genetic variance of erythrocyte parameters in adult male twins

Erythrocyte count, hematocrit, mean corpuscular volume and reticulocyte counts were measured in 59 pairs of monozygotic (MZ) and 69 pairs of dizygotic (DZ) adult, Caucasian male twins. The means of MZ and DZ twins were not significantly different for any of the traits measured. Erythrocyte count and mean corpuscular volume had significant estimates of genetic variance (P < 0.05).
Capecitabine plus oxaliplatin in metastatic colorectal cancer.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES 1. Porschen R, Arkenau H-T, Kubicka S, et al: Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: A final report of the AIO colorectal study group. J Clin Oncol 25:4217-4223, 2007 2. Cassidy J, Clarke C, Diaz-Rubio E, et al: XELOX compared to FOLFOX4: Survival and response results from XELOX-1/NO16966, a randomized phase III trial of first-line treatment for patients with metastatic colorectal cancer (MCRC). J Clin Oncol 25:18s, 2007 (suppl; abstr 4030) 3. Saltz L, Clarke C, Diaz Rubio E, et al: Bevacizumab (Bev) in combination with XELOX or FOLFOX 4: Updated efficacy results from XELOX-1/NO16966, a randomized phase III trial in first-line metastatic colorectal cancer [slideset]. J Clin Oncol 25:18s, 2007 (suppl; abstr 4028)
Blue Tits use fledgling quantity and quality as public information in breeding site choice.

Public information (PI), which is the information that can be derived from the behavior and performance of conspecifics, has been demonstrated to be used in many fitness-enhancing decisions. In the context of breeding habitat choice, PI use has been called "habitat copying. " We experimentally tested the existence of habitat copying in the Blue Tit (Cyanistes caeruleus), a nonmigratory, short-lived hole-nesting bird. We manipulated the mean number of fledglings raised locally (quantity) and their condition (quality) as components of PI by transferring nestlings from Decreased (D) patches to Increased (I) patches. Our manipulations caused a negative relationship between fledgling quantity and quality that does not exist naturally: I patches had a higher number of fledglings that were in poorer condition, whereas D patches had a lower number in better condition. Control (C) patches, whether manipulated or not, had intermediate levels in terms of fledgling quantity and quality. Adult emigration the following year was higher from D than from C or I patches. Similarly, adult dispersal distance decreased for individuals coming from D to C to I patches. This suggests that resident breeders rely mainly on fledgling quantity to make emigration decisions. Emigration patterns of juveniles did not vary in relation to our patch manipulation. Immigration rates were higher and similar in I and D patches than in C patches. Hence, immigrant Blue Tits seem to rely on one of the manipulated components of PI and are insensitive to the discrepancy between fledgling quantity and quality. This shows that even nonmigratory species, such as Blue Tits, may use PI in their dispersal decisions but weigh its components differently for emigration and immigration. Differences among species in the importance of PI in breeding habitat choices may be explained by differences in life histories.
The Duration of Exposure to HIV Modulates the Breadth and the Magnitude of HIV-Specific Memory CD4+ T Cells

The impact of exposure to Ag on the development and maintenance of human CD4+ memory T cells in general and HIV infection in particular is partially understood. In this study, we measured HIV-specific CD4+ T cell proliferative responses against HIV proteins and derived peptides one year after highly active antiretroviral therapy initiation in 39 HIV-infected patients who initiated therapy at different times following infection. We show that a brief exposure to HIV of <1 month does not allow the generation of significant detectable frequencies of HIV-specific CD4+ memory T cells. Patients having prolonged cumulative exposure to high viral load due to therapy failures also demonstrated limited HIV-specific CD4+ T cell responses. In contrast, patients exposed to significant levels of virus for periods ranging from 3 to 18 mo showed brisk and broad HIV-specific CD4+ T cell responses 1 year following the onset of therapy intervention. We also demonstrate that the nadir CD4+ T cell count before therapy initiation correlated positively with the breadth and magnitude of these responses. Our findings indicate that the loss of proliferative HIV-specific CD4+ T cell responses is associated with the systemic progression of the disease and that a brief exposure to HIV does not allow the establishment of detectable frequencies of HIV-specific memory CD4+ T cells.