Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Cdk2 activity decreases Aurora-A kinase centrosomal localization and prevents centrosome amplification in breast cancer cells

Centrosome amplification plays a key role in the origin of chromosomal instability (CIN) during cancer development and progression. In this study, MCF-7 breast cancer cell lines harboring abrogated p53 function (vMCF-7DNp53) were employed to investigate the relationship between induction of genotoxic stress, activation of cyclin-A/Cdk2 and Aurora-A oncogenic signalings and development of centrosome amplification. Introduction of genotoxic stress in the vMCF-7DNp53 cell line by treatment with hydroxyurea (HU) induced centrosome amplification that was mechanistically linked to Aurora-A kinase activity. In cells carrying defective p53, the development of centrosome amplification also occurred following treatment with another DNA damaging agent, methotrexate. Importantly, we demonstrated that Aurora-A kinase-induced centrosome amplification was mediated by Cdk2 kinase since molecular inhibition of Cdk2 activity by SU9516 suppressed Aurora-A centrosomal localization and consequent centrosome amplification. In addition, we employed vMCF-7DRaf-1 cells that display high levels of endogenous cyclin-A and demonstrated that molecular targeting of Aurora-A by Alisertib reduces cyclin-A expression. Taken together, these findings demonstrate a novel positive feed-back loop between cyclin-A/Cdk2 and Aurora-A pathways in the development of centrosome amplification in breast cancer cells. They also provide the translational rationale for targeting ‘druggable cell cycle regulators’ as an innovative therapeutic strategy to inhibit centrosome amplification and CIN in breast tumors resistant to conventional chemotherapeutic drugs.
Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection

Background: We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Methods: Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. Results: We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up (P < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites (P < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. Conclusions: These results support that the airway epithelial field of lung cancer–associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection.
Approach for Selection of a Synthesis Procedure of GeO 2 Ultra-small Nano Particles and Its Characterization

A rigorous study of germanium oxide nano-particle synthesis is done by hydrothermal method. An optimum synthesis condition to obtain the stable and ultra-small size as of 10 nm of the material is determined by characterizing the prepared samples with X-Ray diffraction pattern analysis and TEM. The sample with smallest particle size is also characterized with HRTEM, PL and FTIR spectroscopy. The characterization results are analyzed accordingly. The most remarkable feature of the ultra small sized sample as observed is the current-voltage characteristic, which has been explained with oxygen vacancy phenomenon.
Measurement of the D/H, 18O/16O, and 17O/16O Isotope Ratios in Water by Laser Absorption Spectroscopy at 2.73 μm

A compact isotope ratio laser spectrometry (IRLS) instrument was developed for simultaneous measurements of the D/H, 18O/16O and 17O/16O isotope ratios in water by laser absorption spectroscopy at 2.73 μm. Special attention is paid to the spectral data processing and implementation of a Kalman adaptive filtering to improve the measurement precision. Reduction of up to 3-fold in standard deviation in isotope ratio determination was obtained by the use of a Fourier filtering to remove undulation structure from spectrum baseline. Application of Kalman filtering enables isotope ratio measurement at 1 s time intervals with a precision (<1‰) better than that obtained by conventional 30 s averaging, while maintaining a fast system response. The implementation of the filter is described in detail and its effects on the accuracy and the precision of the isotope ratio measurements are investigated.
Plenary Lecture: Strategies for skeletal health in the elderly

Osteoporosis is a common disease in the elderly, and the fractures that result from this disorder affect 40 % of women and 14 % of men over the age of 50 years. The risk of fracture relates to bone mineral density and the risk of falling, among other factors. Low bone mineral density in the elderly can result from either low peak bone mass or accelerated bone loss, or a combination of the two. Nutritional factors play a role in both the attainment of peak bone mass and in the rate of age-related bone loss. The main determinants of peak bone mass are genetic factors, early-life nutrition, diet and exercise. Of the nutritional factors Ca, and particularly milk, are the most important contributors to peak bone mass. Some of these factors may interact; for example, a low dietary Ca in addition to an unfavourable vitamin D receptor gene polymorphism may result in low peak bone mass. The age-related changes in bone mass may also have a genetic basis, but deficiency of oestrogen is a major contributor. In addition, undernutrition is common in the elderly, and lack of dietary protein contributes both to impaired bone mineral conservation and increased propensity to fall. There is a decreased ability of the intestine to adapt to a low-Ca diet with increasing age. Other dietary factors include vitamin K, Zn and fruit and vegetables. Adequate nutritional status, particularly of Ca and vitamin D, is essential for the successful pharmaceutical treatment of osteoporosis. Thus, strategies for enhancing skeletal health in the elderly must begin in early childhood, and continue throughout life.
Surgery for Chronic Traumatic Atlantoaxial Dislocation Associated With Myelopathy

Study Design: A retrospective study. Objective: To evaluate the outcomes of myelopathy caused by atlantoaxial dislocation (AAD). Summary of Background Data: No reports to date have accurately evaluated the results of surgery for delayed myelopathy for patients with chronic AAD. Thus, the appropriate surgical time and methods of decompression and fusion remain a hot debate. Materials and Methods: In our study, 18 patients underwent decompression, fixation, and fusion. Demographic data, operation time, blood loss, and complications were evaluated. The Japanese Orthopedic Association Scale, severity of disability and visual analogue scale were evaluated. The fusion rate, space available for the cord, instability index, cord compression index, and cord decompression rate were also assessed. Results: The average time of operation was 248±50 minutes, and blood loss was 350±200 mL. Five patients in grade I maintained their neurological status, and the others had improved neurological status. With average follow-up time of 15.3±9.6 months, the Japanese Orthopedic Association score improved, the visual analogue scale score decreased, the space available for the cord improved, and the instability index and cord compression index decreased. Cord decompression rate was 65.9%. Fusion rate reached 83%. Conclusions: There is a high risk of delayed myelopathy for patients with AAD who do not undergo timely surgical treatment. There is no need for complete reduction for treatment of chronic AAD. Whether it can be reduced or not, sufficient decompression and solid fusion for AAD are required. Both C1–C2 fusion for reducible dislocation and occipital-cervical fusion for irreducible dislocation have satisfactory outcomes.
Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer

Protein‐coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial‐mesenchymal‐transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial‐to‐mesenchymal transition and enhancing the tumor‐initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc.
Induced Sputum as a Diagnostic Tool in Pneumonia in Under Five Children—A Hospital-based Study

Objective The objective of this articlewas to study the success, tolerability of sputum induction and the bacterial isolates of induced sputum in children aged <5 years. Methods The cross-sectional study included 120 hospitalized children aged 1-59 months meeting WHO criteria for pneumonia. Sputum induction was performed using hypertonic (3%) saline. Results Mean age of the subjects was 19.5 months (2-59 months). Overall success of sputum induction was 53.3% and highest (64.28%) in 37-59 months age group. Adverse events such as tachypnea, hypoxemia (SpO2 <90) and vomiting were observed in 41.6, 17.5 and 15.8%, respectively. A potential pathogen was isolated in 45 (70.3%) of 64 cases with good quality sputum. Klebsiella pneumoniae was the commonest (38.2%) followed by Streptococcus pneumoniae (14.8%) and others. Conclusion Sputum induction in young children is safe and feasible in Indian settings. While the success was limited, bacterial yield was high.
Planning of Arthroplasty in Dysplastic Hips

Hip dysplasia is one of the major conditions leading degenerative hip arthritis in early adulthood. Devolopmental insuffuciency of bony structures yields asymetric ball and socket formation, which usually associated with trophic changes and instability. Total hip joint replacement has successfull results in patients with hip dysplasia in adulthood. The major goal of the treatment is rebuilding of a new stable artificial joint with painless range of motion. There is a need of a meticulous preoperative planning assessing the anatomic severity of the pathology, which is consisted of involved bony and soft tissue components. Limb length discrepency, quality of bone stock, muscle atrophies, weakness and contractures should be evaluated before surgery. There are several classifications for assesment of acetabuar dysplasia. However, we are aware of a combined clasification or comprehensive allgorithym for assesment of all components of pathology in unisom. Current devolopments in the field of radiology like Three Dimensional (3d) Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) allowed assesment of all component of hip dysplasia preoperatively. Metaphyseal and acetabular bone stock and structure, anteversion degrees and soft tissues has to be taken in consideration. The aim of this chapter is to review the present classifications and reported experiences on hip dysplasia and discuss the value of missing parts. The preoperative planning process were also reviewed regarding the role of modern radiologic examination techniques on current surgical and clinical applications.
To Wait in Tier 1 or Intervene Immediately

This randomized controlled experiment compared the efficacy of two response-to-intervention (RTI) models—typical RTI and dynamic RTI—and included 34 first-grade classrooms (n = 522 students) across 10 socioeconomically and culturally diverse schools. Typical RTI was designed to follow the two-stage RTI decision rules that wait to assess response to Tier 1 in many districts, whereas dynamic RTI provided Tier 2 or Tier 3 interventions immediately according to students’ initial screening results. Interventions were identical across conditions except for when intervention began. Reading assessments included letter-sound, word, passage reading, and teacher-reported severity of reading difficulties. An intent-to-treat analysis based on multilevel modeling indicated an overall effect favoring the dynamic RTI condition (d = .36); growth curve analyses demonstrated that students in dynamic RTI showed an immediate score advantage and that effects accumulated across the year. Analyses of standard score outcomes confirmed that students in the dynamic condition who received Tier 2 and Tier 3 ended the study with significantly higher reading performances than students in the typical condition. Implications for RTI implementation practice and future research are discussed.
Nutrition-related practices in kindergartens in the context of changes to legal regulations on foodstuffs used in canteen menus for children

Background In order to improve the quality of nutrition in care and educational institutions, in year 2015 a restrictive law regulation was introduced. The following year this regulation was withdrawn, and a new legal policy has been introduced. However, data on the impact of these legislations on nutrition in kindergartens are lacking. Objective The aim of the study was to evaluate the compliance with mandatory nutrition recommendations in preschools. Material and methods The study included 706 institutions. Data were collected during the periods when two consecutive Regulation of the Minister of Health were in force (I - 01.09.2015 - 31.08. 2016 and II - 01.09.2016 to 30.05.2017). Data were obtained by face-to-face interviews with staff with a validated questionnaire. Parameters characterizing the quality of nutrition were analyzed with focus on compliance with legal regulations. 706 decade’s menus and 7060 daily inventory reports were analyzed to verify information on vegetables and fruit supply, frequency of frying and type of fat used, sweetening and salting practices. Statistical significances were determined in Statistica 13.1 with t-Student and Chi2 tests (p< 0.05). The study included 706 institutions. Data were collected during the periods when two consecutive Regulation of the Minister of Health were in force (I - 01.09.2015 - 31.08. 2016 and II - 01.09.2016 to 30.05.2017). Data were obtained by face-to-face interviews with staff with a validated questionnaire. Parameters characterizing the quality of nutrition were analyzed with focus on compliance with legal regulations. 706 decade’s menus and 7060 daily inventory reports were analyzed to verify information on vegetables and fruit supply, frequency of frying and type of fat used, sweetening and salting practices. Statistical significances were determined in Statistica 13.1 with t-Student and Chi2 tests (p< 0.05). Results The preschools have implemented regulations concerning the supply of fresh fruit and vegetables (~93%), the amount of fried dish per week (~75%), and the use of suitable frying fat (~95%). About half of institutions managed to serve vegetables and/or fruits in every meal. Compliance with the regulations on sweetening and salting was unsatisfactory: about ¼ of institutions used banned sugar, and 46% regular salt. Conclusions Legislations influenced nutrition practices in preschools, but additional support is needed to bring all institutions into compliance with the current policies. The current law regulations are general, and allow a great flexibility in planning menus, which might has an adverse effect on menus quality. Therefore, nutrition education and more detailed mandatory nutrition standards for kindergartens are crucial.
Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels: Fast Pyrolysis and Hydrotreating Bio-Oil Pathway

This report describes a proposed thermochemical process for converting biomass into liquid transportation fuels via fast pyrolysis followed by hydroprocessing of the condensed pyrolysis oil. As such, the analysis does not reflect the current state of commercially-available technology but includes advancements that are likely, and targeted to be achieved by 2017. The purpose of this study is to quantify the economic impact of individual conversion targets to allow a focused effort towards achieving cost reductions.
A novel peptide Phylloseptin‐PBu from Phyllomedusa burmeisteri possesses insulinotropic activity via potassium channel and GLP‐1 receptor signalling

Insulin, as one of the most important hormones regulating energy metabolism, plays an essential role in maintaining glucose and lipid homeostasis in vivo. Failure or insufficiency of insulin secretion from pancreatic beta‐cells increases glucose and free fatty acid level in circulation and subsequently contributes to the emergence of hyperglycaemia and dyslipidaemia. Therefore, stimulating the insulin release benefits the treatment of type 2 diabetes and obesity significantly. Frog skin peptides have been extensively studied for their biological functions, among which, Phylloseptin peptides discovered in Phyllomedusinae frogs have been found to exert antimicrobial, antiproliferative and insulinotropic activities, while the mechanism associated with Phylloseptin‐induced insulin secretion remains elusive. In this study, we reported a novel peptide named Phylloseptin‐PBu, isolated and identified from Phyllomedusa burmeisteri, exhibited dose‐dependent insulinotropic property in rat pancreatic beta BRIN‐BD11 cells without altering cell membrane integrity. Further mechanism investigations revealed that Phylloseptin‐PBu‐induced insulin output is predominantly modulated by KATP‐[K+] channel depolarization triggered extracellular calcium influx and GLP‐1 receptor initiated PKA signalling activation. Overall, our study highlighted that this novel Phylloseptin‐PBu peptide has clear potential to be developed as a potent antidiabetic agent with established function‐traced mechanism and low risk of cytotoxicity.
Improving the start-up behaviour of TCP-friendly media transmissions

The Internet has built its success story to a large degree on the Transmission Control Protocol (TCP). Sin still represents the by far most important transport protocol in the current Internet traffic mix, new applica like media streaming need to take into account the social rules implied by TCP’s congestion control algor i.e., they need to behave TCP-friendly. One problem of this insight is that these new applications are not alw well served by inheriting TCP’s transmission scheme. In particular, TCP’s initial start-up behaviour is a pro for streaming applications. In this paper, we try to address this problem by proposing a reflective server design which allows to do inter-session congestion control, i.e., to share network performance experiences betwe sions to make informed congestion control decisions. Since our target application is media streaming, w the design in the framework of a media server, which means in particular that we employ not TCP itself TCP-friendly transmissions scheme.
A glimpse is not a glimpse: Differential processing of flashed scene previews leads to differential target search benefits

What information can we extract from an initial glimpse of a scene and how do people differ in the way they process visual information? In Experiment 1, participants searched 3-D-rendered images of naturalistic scenes for embedded target objects through a gaze-contingent window. A briefly flashed scene preview (identical, background, objects, or control) preceded each search scene. We found that search performance varied as a function of the participants’ reported ability to distinguish between previews. Experiment 2 further investigated the source of individual differences using a whole-report task. Data were analysed following the “Theory of Visual Attention” approach, which allows the assessment of visual processing efficiency parameters. Results from both experiments indicate that during the first glimpse of a scene global processing of visual information predominates and that individual differences in initial scene processing and subsequent eye movement behaviour are based on individual differences in visual perceptual processing speed.
Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)

Background To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration ClinicalTrials.gov: NCT01538381.