Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody-targeted liposomes in cancer therapy and imaging

Background: Targeted liposomes can be broadly defined as liposomes that are engineered to interact with a particular population of cells with the objective of delivering a payload or increasing their retention within the targeted cell population by means of a chemical interaction with cell-surface molecules or other tissue-specific ligands. Objective: The authors review recent advances in the field with an emphasis on pre-clinical studies and place them in the context of historical developments. Methods: The review focuses on immunoliposomes (antibody-mediated targeting) as these constructs are presently the most prevalent. Conclusion: The field has advanced in tandem with advances in liposome design and antibody and protein engineering. Targeted liposomes have been used in diagnosis to deliver magnetic resonance contrast agents and radionuclides for magnetic resonance and nuclear medicine imaging, respectively. They have been used in gene therapy to deliver a variety of gene expression modifiers, including plasmids, anti-sense oligonucleotides and short interfering RNA. Targeted liposomes provide a delivery advantage over untargeted liposomes not because of increased localization to tumor sites but because of increased interaction with the target cell population once localized to the tumor site. The increased interaction can take on the form of fusion with the cellular membrane or internalization by endocytosis. To the extent that the spatial distribution of targeted liposomes within a solid tumor may become more non-uniform than has been found for untargeted liposomes, this may be a drawback. However, systematic comparisons of the spatial distribution in tumors of targeted versus untargeted liposomes have yet to be performed. The majority of reported studies have been in the area of chemotherapy delivery. Their use in radionuclide and chemo- and radiosensitizer delivery is just emerging. Multifunctional liposomes containing ‘layered functionalities’ could potentially be the future direction in targeted liposome-based therapy.
A feasibility study of photosensor charge signal transmission to preamplifier using long cable for development of hybrid PET-MRI.

PURPOSE A new positron emission tomography (PET) detector signal processing method, the charge signal transmission approach, is proposed for the development of a hybrid PET-magnetic resonance imaging (MRI). A number of experiments were performed to demonstrate that the Geiger-mode avalanche photodiode (GAPD) charge output could be transmitted to a preamplifier using a long cable without degrading the PET signal performance. METHODS A PET module consisted of LYSO and a GAPD with a 4 x 4 array. The GAPD output was transmitted to the preamplifier through flexible flat cables. The effect of the cable length on the PET performance was examined using seven different lengths ranging from 10 to 300 cm outside and inside the 7 T animal MRI. Four parameters (rise time, fall time, amplitude, and area of the preamplifier output) were measured as a function of the cable length using a 10 GS/s oscilloscope and three parameters (photopeak position, energy resolution, and time resolution) were measured using a 100 MS/s DAQ unit. The effect of the cable length on the MR phantom images was investigated. In addition, the effect of the PET module configuration on its temperature stability was assessed by acquiring the energy and time spectra. RESULTS There were no significant changes in the PET module performance as a function of the cable length, both outside and inside MRI. The performance changes in energy information, such as the amplitude, area, photopeak position, and energy resolution, were <3% with cable lengths ranging from 10 to 300 cm and the change in the time resolution was <6%. There were no obvious artifacts or changes in the line profile in the MR phantom images. Moreover, no manifest changes in the photopeak position and coincidence counting rate were observed in the PET modules employing the charge signal transmission approach, whereas considerable degradation of the PET module performance was observed in the voltage signal transmission approach. CONCLUSIONS This study demonstrated that it is feasible to design a hybrid PET-MRI using the charge signal transmission approach, which is expected to have more advantages than other approaches.
Cervical intraepithelial neoplasia in young women

Summary The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 – 20 years with a histological diagnosis of CIN during the years 1999 – 2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67, 5%) had CIN1 and 26 (32, 5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 – 20 years. Nevertheless, close monitoring is mandatory, as 10 – 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety.
Cloning, characterization and phylogenetic relationships of cel5B, a new endoglucanase encoding gene from Thermobifida fusca

Thermobifida fusca, a thermophilic, aerobic, cellulolytic bacterium has a highly complex cellulase system comprising three endoglucanases, two exoglucanases and one processive endoglucanase. Zymogram analysis indicated that additional cellulases may exist in T. fusca strain TM51, therefore a TM51 expression library was prepared in Streptomyces lividans TK24 and screened for hydrolases. A new endoglucanase gene, named Tf cel5B, was identified. Heterologous Cel5B, produced in S. lividans, had temperature and pH optima of 77 °C and 8.2, respectively and retained more than 60% of its activity after 24 h incubation at 60 °C. Domain analysis revealed an N‐terminal catalytic domain with homology to known endoglucanases in family GH5 and a C‐terminal cellulose binding module III domain (CBD).
A Specific Distortion Pattern of Flash ADCs Identified by Discriminating Time-Domain Analysis

This paper reports a specific error pattern which is observed in several flash analog-to-digital converters (ADCs). The pattern is recognized in reconstructed waveforms like a notch that appears after every peak and bottom of the input. The power of the error is usually so small that it is hard to recognize in the frequency domain, even when the notch is easily visible in the time domain. We have identified the phenomena by elaborate time-domain method that we call “Euclidean reordering. ” It is a kind of waveform reconstruction technique with associated techniques that make the method powerful and general for various ADC analyses, not limited for flash ADCs. The one-clock previous wave plot with the reconstructed waveform is one of associated techniques that indicates the dog-tooth positions at their crossings. We assume hysteresis of comparators as its mechanism and show several clues that support the assumption.
RDF Big Data Management on top of Spark

Modern information and knowledge-centric applications produce, store, integrate, query, analyze and visualize rapidly growing data sets. Traditional data processing technologies (data management and warehousing systems) are inadequate for processing this data and for responding to the new Big Data challenges (the Four+ V’s). A first important challenge related to data volume and velocity concerns data and processing scalability which is achieved through generic massively distributed parallel data processing architectures like Hadoop , Spark 4 and Flink . A second challenge related to data variability concerns the definition and implementation of flexible semi-structured / semantic data models and languages for facilitating complex semantic data representation, integration and access as a complement to traditional structured SQL database systems (noSQL). The Resource Description Framework (RDF) is one of the first data models for modeling and processing this kind of data. Some relevant application examples are the Semantic Web’s Linked Open Data (LOD) cloud which contains over 60 billions RDF triples or the data originating from Schema.org annotations in Web documents.
Improved Lumbar Vertebral Interbody Fusion Using rhOP-1: A Comparison of Autogenous Bone Graft, Bovine Hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in Sheep

Study Design. After disc removal and monosegmental instrumentation of the sheep lumbar spine, interbody fusion was compared for 6 months after administration of autogenous bone graft, hydroxylapatite, or rhOP-1. Objective. To determine whether the use of rhOP-1 or hydroxylapatite would improve on the intercorporal fusion achieved by autologous bone grafting. Summary of Background Data. Spinal fusion often fails or shows loss of correction despite large-scale conventional techniques using posterior and anterior access. Also, additional operations to obtain bone grafts are required, which increase morbidity and strain for the patient, but do not always provide bone with sufficient primary stability and high osteogenic potential. Methods. Vertebral fusion quality was examined by plain radiograph at 4-week intervals, by scintigraphy at 3 and 6 months, and by computed tomography scan, magnetic resonance imaging, biomechanical testing, and histologic evaluation. Results. All examination methods demonstrated superior fusion after administration of rhOP-1, with radiologic fusion apparent at 4 months. Autologous bone grafts eventually produced bony healing in most cases, albeit of a lower quality than with rhOP-1. Hydroxylapatite use led only to the formation of a tight pseudarthrosis. Conclusions. The results indicate that rhOP-1 use is an appropriate method for improving interbody fusion in the sheep spine. In addition to offering the potential for improved bone healing, rhOP-1 use may permit less invasive surgery such as transpedicular fusion and the use of cages.
Dramatic Increase in Prevalence of Fecal Carriage of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae during Nonoutbreak Situations in Spain

ABSTRACT The occurrence of extended-spectrum β-lactamase (ESBL)-producing isolates has increased worldwide. Fecal carriage of ESBL-producing isolates has mainly been detected in nosocomial outbreaks, and few studies have evaluated fecal carriage during nonoutbreak situations and among patients in the community. We have studied the prevalence of ESBLs in 1,239 fecal samples from 849 patients (64.1% of whom were ambulatory) in 1991 and have compared the prevalence data with those obtained in 2003 for 400 fecal samples from 386 patients (75.9% of whom were ambulatory) and 108 samples from independent healthy volunteers. Samples were diluted in saline and cultured in two MacConkey agar plates supplemented with ceftazidime (1 μg/ml) and cefotaxime (1 μg/ml), respectively. Colonies were screened (by the double-disk synergy test) for ESBL production. The clonal relatedness of all ESBL-producing isolates was determined by pulsed-field gel electrophoresis with XbaI digestion; and the ESBLs of all ESBL-producing isolates were characterized by isoelectric focusing, PCR, and sequencing. The rates of fecal carriage of ESBL-producing isolates increased significantly (P < 0.001) in both hospitalized patients and outpatients, from 0.3 and 0.7%, respectively, in 1991, to 11.8 and 5.5%, respectively, in 2003. The rate of occurrence of ESBL-producing isolates among healthy volunteers was 3.7%. All ESBL-producing isolates recovered in 2003 were nonepidemic clones of Escherichia coli. ESBL characterization revealed an increasing diversity of ESBL types: TEM-4 and CTX-M-10 were the only enzymes detected in 1991, whereas TEM-4, TEM-52, SHV-12, CTX-M-9, CTX-M-10, CTX-M-14, and a CTX-M-2-like enzyme were recovered in 2003. The ESBL-producing isolates recovered from outpatients in 2003 corresponded to a CTX-M-9-type cluster (62.5%) and SHV-12 (31.2%), whereas TEM-4 was detected only in hospitalized patients. The frequencies of coresistance in isolates recovered in 2003 were as follows: sulfonamide, 75%; tetracycline, 64.3%; streptomycin, 57.1%; quinolones, 53.5%; and trimethoprim, 50%. The increased prevalence of fecal carriage of ESBL-producing isolates during nonoutbreak situations in hospitalized patients and the establishment of these isolates in the community with coresistance to non-β-lactam antibiotics, including quinolones, represent an opportunity for these isolates to become endemic.
Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin

NKG2D is a recently described activating receptor expressed by both NK cells and CTL. In this study we investigated the role of NKG2D in the natural cytolysis mediated by NK cell clones. The role of NKG2D varied depending on the type of target cells analyzed. Lysis of various tumors appeared to be exclusively natural cytotoxicity receptors (NCR) dependent. In contrast, killing of anothergroup of target cells, including not only the epithelial cell lines HELA and IGROV‐1, but also the FO‐1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even normal PHA‐induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell clones expressing low surface densities of NCR (NCRdull) could lyse these tumors in an exclusively NKG2D‐dependent fashion. Remarkably, notall of these targets expressed MICA/B, thus implying the existence of additional ligands recognized by NKG2D, possibly represented by GPI‐linked molecules. Finally, we show that the engagement of different HLA class I‐specific inhibitory receptors by either specific antibodies or the appropriate HLA class I ligand led to inhibition of NKG2D‐mediated NK cell triggering.
Effects of dentin surface treatments including Er,Cr:YSGG laser irradiation with different intensities on the push-out bond strength of the glass fiber posts to root dentin

Abstract Objective. Intra-canal post systems are commonly used to restore root-filled teeth. Bond strengths of the posts can be affected by various surface treatments of the post or the dentin. The aim of this study was to evaluate the effects of dentin surface treatments including erbium-chromium; yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser irradiation with different intensities on the push-out bond strength of the glass fiber posts to root dentin. Materials and methods. Forty single-rooted human maxillary incisors were filled and post spaces were prepared. After these procedures, the specimens were divided randomly into four groups according to the dentin surface treatments, as follows: (i) untreated surface (control), (ii) 1W Er,Cr:YSGG laser application, (iii) 2W Er,Cr:YSGG laser application and (iv) 3W Er,Cr:YSGG laser application. Then the posts were cemented into the root canals using dual-cured resin cement. Bonded specimens were cut into 1-mm-thick slices and push-out tests were performed using a universal testing device. All specimens were loaded until fracture and the failure modes were evaluated with a stereomicroscope at 32× magnification. Representative specimens were analyzed by scanning electron microscopy. Data were analyzed using a one-way ANOVA, Tukey and Wilcoxon tests. Results. The bond strength values ranged from 3.22–4.68 MPa. There were no statistically significant differences among the groups, regardless of the different levels. The coronal and middle levels of the post space had significantly higher bond strength values compared with the apical level (p < 0.05). Conclusion. Er,Cr:YSGG laser irradiation with different intensities did not increase the bond strength of the fiber posts to the root canal dentin walls.
Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis. Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.
BICAMS in the Argentine population: Relationship with clinical and sociodemographic variables

ABSTRACT The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed to provide valid assessment of cognitive impairment in multiple sclerosis (MS). The relationship between clinical and social variables and cognitive disorders has been extensively studied, but primarily in developed countries with a focus on other cognitive measures or batteries. The objectives of this study were to analyze the relationship between the BICAMS data and key clinical and sociodemographic variables in the Argentine MS population. A total of 50 MS patients were administered the Argentinean BICAMS Battery, comprised of the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test I (CVLT I), and the Brief Visuospatial Memory Test Revised (BVMTR). Disease progression, fatigue, depression, self-reported and informant report cognitive status, and employment status were assessed. Disease progression and employment status were most strongly associated with overall BICAMS performance (η2 effect size values ranging from .302 to .624, all comparisons statistically significant). Informant rating of patient cognition, age, depression, disease duration, fatigue, and work hours were significantly associated as well. Gender, years of education, and patient-reported cognitive status were nonpredictive. A similar pattern was seen at the individual test level, with more variables related to the SDMT and CVLT I than BVMTR. BICAMS is strongly associated with overall disease progression and employment status.
OPHTHALMIC CHANGES FROM AGE OF 10 TO 18 YEARS

The present report on vitreous and axial length completes an analysis of changes in eye size during adolescence. The sample is divided into 70 with low birth weight (< 2000 g) and 67 full‐term controls (FT). 1) Contrary to classical statements regarding early arrest of eye growth, a basic ‘pubertal’ axial growth of about 0.4– 0.5 mm is found in refractively static eyes. Eyes with progressive myopia elongate even more, due mainly to vitreous elongation. 2) The previously reported 10‐year LBW ocular size deficit remains an adult feature, even in seemingly normal eyes. There is a parallel permanent lack of catching‐up also regarding height, head circumference, and some other anthropometric parameters. 3) Two classical rules of thumb are discussed: a) 1 mm axial length change coincides with 3 D refractive change, and b) that of 24 mm as the emmetropic eye length. Although tenacious, bot statements have to be modified – according to biological variation and the weak correlation between most refractive parameters.
Stability analysis for systems with nested backlash and saturation operators

This paper is concerned with the problem of stability analysis for a certain class of nonlinear systems resulting from nested backlash and saturation operators. Constructive conditions based on LMIs, to ensure the local or global stability of the system, are proposed by using some suitable Lyapunov functional, generalized sector conditions and polytopic representation. The associated set of all the equilibrium points is precisely defined.
On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients

Despite the increased use of molecular diagnostics, the extent to which patients who have these tests harbor potentially actionable aberrations is unclear. We retrospectively reviewed 439 patients with diverse cancers, for whom next-generation sequencing (mostly 236-gene panel) had been performed. Data pertaining to the molecular alterations identified, as well as associated treatment suggestions (on- or off-label, or experimental), were extracted from molecular diagnostic reports. Most patients (420/439; 96%) had at least one molecular alteration: 1,813 alterations (in 207 distinct genes) were identified [the majority being mutations (62%) or amplifications (29%)]. The three most common gene abnormalities were TP53 (44%), KRAS (16%), and PIK3CA (12%). The median number of alterations per patient was 3 (range, 0–16). Nineteen patients (4%) had no alterations; 48 patients (11%) had only one alteration; and 372 patients had two or more abnormalities (85%). The median number of potentially actionable anomalies per patient was 2 (range, 0–8). Most patients (393/439; 90%) had at least one potentially actionable alteration, and in all these cases the aberration could at least be targeted by an experimental drug in a clinical trial. A total of 307 patients (70%) had an alteration that was actionable with an approved drug, but in only 89 patients (20%) was the drug approved for their disease (on-label). Next-generation sequencing identified theoretically actionable aberrations in 90% of our patients. Many of the drugs are, however, experimental or would require off-label use. Strategies to address drug access for patients harboring potentially actionable mutations are needed. Mol Cancer Ther; 14(6); 1488–94. ©2015 AACR.
Analysis of the activating receptors and cytolytic function of human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation

Patients undergoing allogeneic bone marrow transplantation offer a unique system to analyze NK cell development in vivo. We analyzed NK cells from 23 such patients to assess the acquisition of activating receptors. Four patients displayed an immature NK cell surface phenotype at engraftment, as their cells were CD16–KIR– and NKG2D– but expressed low levels of NKp46, NKp30, 2B4 and NKG2A. These NK cells had particularly low cytolytic activity against the HLA‐class‐I– melanoma F01 cell line and the 721‐221 EBV‐infected B cell line. Moreover, cytoxicity was inhibited upon mAb‐mediated crosslinking of 2B4. Analysis of NK cells at day 30 after bone marrow transplantation revealed the occurrence of both phenotypic and functional maturation. These data are in agreement with a previous in vitro study showing that immature NK cell precursors express CD16, NKG2D and KIR only at a late stage of differentiation and also express inhibitory 2B4. Our present study allows a better understanding of the NK cell differentiation in vivo.