Miracle-dz/UniFAR-FTUs huggingface dataset:
Complementary combinations: what treatments will become key to the battle against acute myelogenous leukemia?

Despite major progress in our understanding of the biology of acute myelogenous leukemia (AML), there have been few advances in therapy. Two-thirds of young adults and 90% of older adults with AML die of their disease [1]. Similarly, long-term outcomes for patients with relapsed/refractory disease and those with secondary AML remain dismal [2]. The remarkable success of the Bcr-Abl tyrosine kinase inhibitor (TKI) imatinib in chronic myelogenous leukemia (CML) validated the concept of oncogene addiction – a phenomenon in which cancer cells are physiologically dependent on the continued activity of specific activated or over expressed oncogenes for maintenance of their malignant phenotype [3] – and ushered in the era of molecularly targeted cancer therapy. Unfortunately, the exclusive dependence of CML cells on signaling through the Bcr-Abl pathway is the exception rather than the rule for malignancies in general, and it quickly became apparent that cotargeting of multiple cooperative survival pathways must be employed to overcome the marked redundancy that exists among them. Indeed, in preclinical studies of glioblastoma multiforme, combinations of TKIs, but not single agents, decreased signaling, cell survival, and anchorage-independent growth [4]. The two-hit theory of leukemogenesis [5] provides a theoretical basis for combining ‘targeted’ agents for AML therapy. Such drugs target pathways directly implicated in neoplastic transformation, in contrast to conventional cytotoxic chemotherapeutic agents, which exert a more general disruptive effect on key cellular structures or processes. Leukemic cells are highly susceptible to strategies in which survival signaling and cell cycle regulatory pathways are simultaneously disrupted. While interest in combining novel agents with cytotoxic chemo therapy to lower the apoptotic threshold persists, the concept of simultaneous disruption of multiple cooperative survival pathways with rational combinations of targeted agents is rapidly gaining ground, and is likely to be a major focus of leukemia research in future years. In this brief editorial, we discuss some of the more promising synergistic combinations of targeted agents currently in development for the treatment of AML.
Dynamic imaging on the high resolution research tomograph (HRRT): non-human primate studies

The high resolution research tomography (HRRT) is currently the most complex human brain scanner due to its ability to detect the gamma depth of interaction, its octagonal geometry, and the large number of crystals (119,808) leading to approximately 4.5 /spl times/ 10/sup 9/ possible lines of response (LORs). Reconstruction of dynamic studies on this scanner is particularly challenging due to the dynamic range of both, number of acquired events per frame and acquisition count rates. Some artifacts have been observed with phantom studies: here we evaluate their impact on time activity curves (TACs) and binding potential (BP) values in realistic scanning situations with the ultimate goal of defining an efficient and accurate image reconstruction protocol. Non-human primate studies were used for this purpose. We compared TACs and BPs obtained from images reconstructed with three different reconstruction algorithms, two different axial spanning configurations and detector normalization factors obtained from two different data sets. We also compared BP values obtained from scans of the same animal performed on the Siemens ECAT 963B and the HRRT under identical conditions. The statistical reconstruction methods produced nearly identical results and the impact of emission/normalization count rate mismatch was found to be effectively negligible. Likewise no image degradation due to increased axial spanning was observed. Data obtained from the analytical method were less robust and in general much more sensitive to noise, thus demonstrating a suboptimal performance of this algorithm. The BP values obtained with the HRRT were by approximately 50% higher compared to those obtained in the ECAT as a result of the increased resolution of this tomograph.
Correlation analysis of the progesterone‐induced sperm acrosome reaction rate and the fertilisation rate in vitro

In this study, we aimed to investigate whether progesterone‐induced acrosome reaction (AR) rate could be an indicator for fertilisation rate in vitro. Twenty‐six couples with unexplained infertility and undergoing in vitro fertilisation (IVF) treatment were involved. On the oocytes retrieval day after routine IVF, residual sperm samples were collected to receive progesterone induction (progesterone group) or not (control group). AR rate was calculated and fertilisation rate was recorded. The correlation between progesterone‐induced AR and fertilisation rate and between sperm normal morphology and 3PN (tripronuclear) were analysed using the Spearman correlation analysis. The AR rate of progesterone group was statistically higher than that of the control group (15.6 ± 5.88% versus 9.66 ± 5.771%, P < 0.05), but not significantly correlated with fertilisation rate (r = −0.053, P > 0.01) or rate of high‐quality embryo development (r = −0.055, P > 0.01). Normal sperm morphology also showed no significant correlation with the amount of 3PN zygotes (r = 0.029, P > 0.01), rate of 3PN zygotes production (r = 0.20, P > 0.01), rate of 3PN embryo development (r = −0.406, P > 0.01), fertilisation rate (r = −0.148, P > 0.01) or progesterone‐induced AR rate (r = 0.214, P > 0.01). Progesterone can induce AR in vitro significantly; however, the progesterone‐induced AR may not be used to indicate fertilisation rate.
Estudio del paciente con infección por VIH

Resumen: el virus de la inmunodeficiencia humana (VIH) es el agente causal del SIDA. Más de 30 millones de persones en el mundo padecen esta infección. Hasta la fecha se han caracterizado dos tipos de virus: el VIH-1, el cual es el tipo que predomina a nivel mundial, y el VIH-2, ubicado hasta el momento sólo en África occidental. El virus infecta hombres y mujeres igualmente y es una causa muy importante de mortalidad en los adultos jóvenes. El VIH es uno de los patógenos humanos más variables genéticamente, lo cual hace el desarrollo de vacunas difícil. La transmisión heterosexual continúa siendo la principal forma de transmisión y corresponde al 85% de todas las infecciones. La introducción al mercado de los inhibidores de proteasa y de los inhibidores no nucleósidos de la transcriptasa reversa en 1995 inició la era de la terapia antirretroviral altamente potente (HAART), lo cual ha tenido como resultado una disminución marcada en la morbilidad y mortalidad asociadas con la enfermedad; sin embargo, la erradicación del virus una vez la persona ha sido infectada, continúa siendo imposible. La comprensión detallada de este agente patógeno es fundamental para el diagnóstico, tratamiento y prevención de la infección.
Ausbruch der Koi-Herpesvirusinfektion in einer großen Karpfenteichwirtschaft in Nordthüringen

Zusammenfassung Gegenstand: Bericht über eine Koi-Herpesvirusinfektion. Material und Methoden: Eine bedeutende Koi-Herpesvirusinfektion, die erstmalig in Thüringen auftrat, wird in ihrem Verlauf beschrieben. Der Nachweis des Virus erfolgte mittels PCR-Untersuchung. Ergebnisse: Die Infektion führte zu schwersten Krankheitsverläufen mit Massenverlusten bei Karpfen aller Altersklassen, wobei es in den K1-Beständen zu Totalverlusten kam. Die Krankheit war ausschließlich auf Karpfen beschränkt. Die erkrankten Bestände wurden tierschutzgerecht getötet und entsorgt. Dem schlossen sich fischereiliche sowie teichhygienische Maßnahmen an. Die direkten Schäden durch Fischverluste und Entsorgungskosten beliefen sich auf 310 000 €. Die Desinfektionskosten betrugen 19 000 €. Die epidemiologischen Erhebungen ergaben, dass die Erkrankung durch den Zukauf latent verseuchter Satzfische eingeschleppt wurde. Die Untersuchungsergebnisse im Jahr 2005 geben Anlass zu der Annahme, dass die Sanierung der Teichwirtschaft von der Krankheit erfolgreich verlief. Klinische Relevanz: Da keine Behandlungen bzw. Immunisierungen möglich sind, bleibt als wichtigste präventive Maßnahme der Zukauf von Satzfischen aus klinisch unverdächtigen, virologisch kontrollierten Betrieben bestehen.
Human bocavirus isolated from children with acute respiratory tract infections in Korea, 2010–2011

Human bocavirus (HBoV) was first recognized in respiratory samples in 2005. The clinical importance of HBoV infection remains unclear. This report describes the clinical features and molecular phylogeny of HBoV isolates in children with acute respiratory infections. Nasopharyngeal aspirates were obtained from 1,528 children with acute respiratory infections between 2010 and 2011. Respiratory samples were screened for HBoV by multiplex PCR. A phylogenetic analysis of the HBoV VP1/VP2 gene was also undertaken. HBoV was detected in 187 (12.2%) of the 1,528 patients with a peak incidence of infection observed in patients aged 12–24 months. Coinfection with other respiratory viruses was observed in 107 (57.2%) of the HBoV‐positive children. The peak of HBoV activity occurred during the month of June in both 2010 and 2011. A higher previous history of wheezing (P = 0.016), a higher frequency of chest retraction (P < 0.001) and wheezing (P = 0.022), a higher respiratory symptom score (P = 0.002), and a longer duration of hospital stay (P = 0.021) were observed in HBoV‐positive children compared with the HBoV‐negative group. Phylogenetic analysis showed all 187 HBoV‐positive isolates were identified as HBoV 1, indicating minimal sequence variations among the isolates. A single lineage of HBoV 1 was found to have circulated in children with acute respiratory infections between 2010 and 2011 and was associated with several clinical characteristics including age, seasonality, and clinical severity with retraction, wheezing, and longer hospitalization. The clinical relevance of the minimal sequence variations of HBoV remains to be determined. J. Med. Virol. 86:2011–2018, 2014. © 2014 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.
Detecting Cognitive Distortions Through Machine Learning Text Analytics

Machine learning and text analytics have proven increasingly useful in a number of health-related applications, particularly in the context of analyzing online data for disease epidemics and warning signs of a variety of mental health issues. We follow in this tradition here, but focus our attention on cognitive distortion, a precursor and symptom of disruptive psychological disorders such as anxiety, anorexia and depression. We collected a number of personal blogs from the Tumblr API, and labeled them based on whether they exhibited distorted thought patterns. We then used LIWC to extract textual features and applied machine learning to the resulting vectors. Our findings show that it is possible to detect cognitive distortions automatically from personal blogs with relatively good accuracy (73.0%) and false negative rate (30.4%).
Surface roughness of heat treated Eucalyptus grandis wood

This study aimed to evaluate surface roughness of heat treated Eucalyptus grandis wood after peripheral planning and sanding performed in directions to the grain and against the grain. For machining tests, workpieces were collected from two different regions in the radial direction, as follows: internal, nearby the pit; external, nearby the bark. Heat treatment was carried out by heating samples at a maximum temperature of 190oC, with total treatment duration of 390 minutes. Heat treated and control samples underwent peripheral planning and sanding tests. The quality of machined surfaces was assessed by means of roughness average (Ra) measurements across and along the grain orientation. Results indicated significant differences in surface roughness as a function of machining feed direction, sandpaper grit size, and heat treatment. Surface roughness has not shown any difference in the radial direction.
Apport de l'échantillonnage aléatoire à temps quantifié pour le traitement en bande de base dans un contexte radio logicielle restreinte

Ces travaux de recherche s’inscrivent dans le cadre de la conception de recepteurs multistandard optimises pouvant traiter des signaux a specifications heterogenes. L’idee est d’appliquer l’echantillonnage aleatoire au niveau de l’etage en bande de base d’un recepteur radio logicielle restreinte afin de tirer profit de son pouvoir d’anti-repliement. La nouveaute dans ces travaux est l’etude analytique de la reduction du repliement spectral par l’echantillonnage aleatoire a temps quantifie, candidat favorable a l’implementation materielle. Une deuxieme contribution concerne aussi l’etude analytique de l’echantillonnage pseudo-aleatoire a temps quantifie (TQ-PRS) dont l’importance reside en sa grande facilite d’implementation materielle. Les formulations theoriques ont permis d’estimer l’attenuation des repliques en fonction du facteur de la quantification temporelle et du facteur du sur-echantillonnage. Les mesures de l’attenuation du repliement spectral ont permis de dimensionner l’etage en bande de base d’une architecture de reception multistandard. Le dimensionnement s’interesse a differentes configurations de l’etage en bande de base regies par les performances du convertisseur analogique numerique (ADC) utilise.Les travaux de recherche ont demontre que l’application du TQ-PRS au niveau de l’ADC mene soit a une reduction de l’ordre du filtre anti-repliement soit a une reduction de la frequence d’echantillonnage. Un bilan global de la consommation de puissance a permis un gain de 30% de la consommation de l’etage en bande de base analogique. En tenant compte du generateur de l’horloge TQ-PRS et de l’etage de selection numerique du canal, ce gain devient 25%.
Analytical TEM Examinations of CoPt-TiO2 Perpendicular Magnetic Recording Media

For this analytical TEM study, nonmagnetic oxygen-rich boundaries were introduced into Co-Pt-alloy perpendicular recording media by cosputtering Co and Pt with TiO2. Increasing the TiO2 content resulted in changes to the microstructure and elemental distribution within grains and boundaries in these films. EFTEM imaging was used to generate composition maps spanning many tens of grains, thereby giving an overall depiction of the changes in elemental distribution occurring with increasing TiO2 content. Comparing EFTEM with spectrum-imaging maps created by high-resolution STEM with EDXS and EELS enabled both corroboration of EFTEM results and quantification of the chemical composition within individual grain boundary areas. The difficulty of interpreting data from EDXS for these extremely thin films is discussed. Increasing the TiO2 content of the media was found to create more uniformly wide Ti- and O-rich grain boundaries as well as Ti- and O-rich regions within grains.
A compact low-power 24 GHz transceiver for radar applications in 0.13 µm CMOS

This paper presents a compact low-power transceiver for 24 GHz radar applications integrated in 0.13 μm CMOS technology. The high integration level includes a low-noise amplifier (LNA), two mixers, on-chip quadrature generation, a voltage-controlled oscillator (VCO), a power amplifier (PA) driver and frequency division by four at a record minimal area of 0.7 mm2. The direct-conversion receiver offers a conversion gain of 12 dB and a DSB noise figure of 5.5 dB, whilst the transmitter provides an output power of -3 dBm with a phase noise of -101 dBc/Hz. The circuit consumes only 88 mW from a single 1.5 V supply.
Determinants of Renal Vascular Resistance in the Dahl Strain of Genetically Hypertensive Rat

SUMMARY Hypertension-resistant (R) rats of the Dahl strain remain normotenslve on diets containing excessive sodium chloride, while hypertension-sensitive (S) rats rapidly become hypertensive when eating the same diet. In the present study, renal hemodynamlcs were investigated in Dahl rats eating normal or high salt chow for 4 weeks. The R rats eating sodium-enriched cbow were found to have significantly lower renal vascular resistance (RVR) than R rats on normal chow; RVR was identical in S rats on either diet. The reason for the failure of S kidneys to exhibit vasodilation during high salt ingestion was explored by examining renal vascular responses to interruption of the renal sympathetic nerves, renal sympathetic nerve stimulation (SNS), and to several vasoactive agents. Changes in RVR to nerve section and to SNS were similar in both strains regardless of diet Renal vascular responses to Intraarteritl norepinephrine were suppressed significantly by high salt intake only in the R rats. Changes in RVR to lntraarterlal angiotensin II were uniformly greater in S than in R rats, but were not altered by salt intake in either strain. Renal vasodilation in response to intraarterial acerylcholine was reduced in R rats on high salt intake, but was not affected by salt intake in S rats. It is concluded that S rats exhibit inappropriately high renal vascular tone during ingestion of excessive salt, and that this alteration is not the result of increased neurogenic activity or increased vascular reactivity to angiotensin II or norepinephrine.
Design and implementation of OFDM transceiver system using M-PSK encoding techniques

Multi-carrier or orthogonal frequency division multiplexing (OFDM) has become the chosen modulation technique for wireless communications because it provides a high data rate wireless transmission. Some examples of applications using OFDM include ETSI BRAN in Europe, IEEE802.11 in United States, and ARIB MMAC in Japan. Therefore, many research centers in the world have specialized teams working in the optimization of OFDM for countless applications. This paper is to demonstrate the concept and feasibility of an OFDM system, and investigate how its performance is changed by varying some of its major parameters by using a MATLAB program to simulate an OFDM system. From the process of this development, the mechanism of an OFDM system can be studied; and with a completed MATLAB program, the characteristics of an OFDM system can be explored.
Leveraging traditional EDI investment using the Internet: a case study

For many large retail companies with many suppliers, the utopian vision of total paperless trading offered by traditional electronic data interchange (EDI), with its attendant efficiencies, has not been realized. Many small but operationally important suppliers lack enthusiasm for traditional EDI because it is expensive, complicated and they stand to gain little from it. This non-compliance prevents the large organization from realizing some of the most significant tactical benefits of EDI such as advanced supply chain reforms. This paper presents a case study of a large retail organization which is approaching this problem by integrating Internet-based EDI with its existing traditional EDI systems using an intelligent gateway. The case study is used to generate propositions about the future significance of Internet EDI.
Comparison of actigraphy with polysomnography and sleep logs in depressed insomniacs

Actigraphy is increasingly used in the assessment and treatment of various clinical conditions, being a convenient and cost‐effective method of capturing bodily movements over long periods of time. This study examined the use of actigraphy in the measurement of sleep of patients with depression and insomnia. Fifty‐four patients diagnosed with a current major depressive episode and chronic insomnia underwent a baseline overnight study with concurrent actigraphic and polysomnography (PSG) monitoring, as well as subjective sleep diaries. Agreement between PSG, actigraphy and sleep diary measurements was evaluated using two‐tailed t‐tests, Pearson’s correlations and the Bland–Altman concordance technique. The only significant difference found between actigraphy and PSG was in latency to persistent sleep, in which actigraphy underestimated sleep latency relative to PSG (P < 0.05). There were moderate positive correlations between actigraphy and PSG for all variables. In contrast, significant differences were observed between sleep diaries and PSG for all sleep variables. Bland–Altman concordance diagrams also demonstrated that, while bias was limited between PSG and the other two measurement types, there were somewhat broad 95% limits of agreement for all sleep variables with both sleep diaries and actigraphy. In summary, actigraphic measurements of sleep more closely approximated those of PSG than did sleep diaries in this sample of depressed insomniacs.
Clinical outcome of treatment with serine-threonine kinase inhibitors in recurrent epithelial ovarian cancer: a systematic review of literature

ABSTRACT Introduction: While serine-threonine kinases (STK) are attractive therapeutic targets in epithelial ovarian cancer, clinical outcomes of STK inhibitors in the management of recurrent disease have not been completely described. Areas covered: A systematic literature review of published clinical studies on STK inhibitors targeting mTOR, MAPK, and aurora kinase pathways in recurrent epithelial ovarian cancer was conducted, revealing 18 clinical trials (497 patients). Pooled analyses were performed to assess treatment response, survival time, and adverse events. Median progression-free survival was 3.4 months in STK inhibitor-based therapy, and the average response rate and clinical benefit rate were 13% and 67%, respectively. Among regimens comprised of only STK inhibitors (11 trials, 299 patients), median progression-free time was 2.7 months, response rate was 10%, and clinical benefit rate was 64%. Compared to single STK inhibitor monotherapy (52.5%), clinical benefit rates significantly improved when STK inhibitors were combined with a cytotoxic agent (71.4%), other class biological agent (74.2%), or an additional STK inhibitor (95.0%) (all, P ≤ 0.002). Expert opinion: STK inhibitor-based therapy showed modest activity for recurrent epithelial ovarian cancer with reasonable clinical benefit rates, suggesting its potential utility for maintaining disease stability if supported by future studies. Efficacy appears greatly improved in appropriately selected patient populations, especially those with low-grade serous ovarian carcinoma, platinum-sensitive disease, cancers with somatic RAS or BRAF mutations, and when used in a combination regimen with a cytotoxic or biological agent.
Comparative evaluation of the intracellular accumulation and DNA binding of idarubicin and daunorubicin in sensitive and multidrug-resistant human leukaemia K562 cells.

BACKGROUND Idarubicin is a new anthracycline, more potent in in vitro models than the common anthracyclines doxorubicin and daunorubicin. The intracellular accumulation and DNA binding of daunorubicin and idarubicin have been studied in human leukaemia K562 cells and their doxorubicin-resistant variant, which presents all features of multidrug resistance. METHODS This was achieved by measuring the decrease of total drug fluorescence during short-term incubation of cell suspensions, directly in the cuvette of a spectrofluorometer; this quenching is due to intercalation of the drug into DNA and represents an evaluation of the active intracellular concentration of the drugs. RESULTS Accumulation of both anthracyclines was reduced in resistant cells when compared to sensitive ones. Accumulation of idarubicin was significantly higher than that of daunorubicin in both cell types. The difference in anthracycline accumulation between sensitive and resistant cells was lower for idarubicin than for daunorubicin. Verapamil increased the accumulation of both anthracyclines in resistant cells, with a more pronounced effect for idarubicin. Preincubation of the cells with either drug did not influence the accumulation of the other one. CONCLUSION It has been shown, with this very rapid technique, that the high potency of idarubicin could be explained, at least in part, by its high level of accumulation, both in sensitive and multidrug-resistant leukaemia cells. This is not due to a lack of activity of P-glycoprotein on idarubicin, but rather to an enhanced influx of this drug compared to daunorubicin.