Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormone receptor status may impact the survival benefit of surgery in stage IV breast cancer: a population-based study

Introduction The role of surgery in stage IV breast cancer is controversial. We used the Surveillance, Epidemiology, and End Results database to explore the impact of surgery on the survival of patients with stage IV breast cancer. Methods In total, 10,441 eligible stage IV breast cancer patients from 2004 to 2008 were included. They were divided into four groups as follows: R0 group (patients who underwent primary site and distant metastatic site resection), primary site resection group, metastases resection group, and no resection group. Results The four groups achieved a median survival time (MST) of 51, 43, 31 and 21 months, respectively, P < 0.001. The Cox proportional hazards model showed that the R0 group, primary resection group and metastases resection group had a good survival benefit, with hazard ratios of 0.558 (95% CI, 0.471-0.661), 0.566 (95% CI, 0.557-0.625) and 0.782 (95% CI, 0.693-0.883), respectively. In the hormone receptor (HR)-positive population, the R0 group (MST = 66 m, 5-year OS = 54.1%) gained an additional survival benefit compared with the primary resection group (MST = 52 m; 5-year OS = 44.9%; P < 0.001). The metastases resection group (MST = 38 m; 5-year OS = 31.7%) survived longer than the no resection group (MST = 28 m; 5-year OS = 22.0%; P < 0.001). In the HR-negative population, the R0 group and primary resection group had a similar survival (P = 0.691), and the metastases resection group had a similar outcome to that of the no resection group (P = 0.526). Conclusion Patients who underwent surgery for stage IV breast cancer showed better overall survival than the no resection group. Cytoreductive surgery could provide a survival benefit in HR+ stage IV breast cancer; however, in the HR- population, extreme caution should be exercised when considering surgery.
Performance Evaluation of Components Using a Granularity-based Interface Between Real-Time Calculus and Timed Automata

To analyze complex and heterogeneous real-time embedded systems, recent works have proposed interface techniques between real-time calculus (RTC) and timed automata (TA), in order to take advantage of the strengths of each technique for analyzing various components. But the time to analyze a state-based component modeled by TA may be prohibitively high, due to the state space explosion problem. In this paper, we propose a framework of granularity-based interfacing to speed up the analysis of a TA modeled component. First, we abstract fine models to work with event streams at coarse granularity. We perform analysis of the component at multiple coarse granularities and then based on RTC theory, we derive lower and upper bounds on arrival patterns of the fine output streams using the causality closure algorithm. Our framework can help to achieve tradeoffs between precision and analysis time.
Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures

Background Guidelines advise periprocedural saline hydration for prevention of contrast induced-acute kidney injury (CI-AKI). We analysed whether 1-hour sodium bicarbonate hydration administered solely prior to intra-arterial contrast exposure is non-inferior to standard periprocedural saline hydration in chronic kidney disease (CKD) patients undergoing elective cardiovascular diagnostic or interventional contrast procedures. Methods We performed an open-label multicentre non-inferiority trial between 2011–2014. Patients were randomized to 1 hour pre-procedure sodium bicarbonate hydration (250 ml 1.4%, N = 168) or 4–12 hours saline hydration (1000 ml 0.9%, N = 165) prior to and following contrast administration (2000 ml of saline total). Primary outcome was the relative serum creatinine increase (%) 48–96 hours post contrast exposure. Secondary outcomes were: incidence of CI-AKI (serum creatinine increase>25% or >44μmol/L), recovery of renal function, the need for dialysis, and hospital costs within two months follow-up. Results Mean relative creatinine increase was 3.1% (95%CI 0.9 to 5.2%) in the bicarbonate and 1.1% (95%CI -1.2 to 3.5%) in the saline arm, mean difference 1.9% (95%CI -1.2 to 5.1%, p-non-inferiority <0.001). CI-AKI occurred in 11 (6.7%) patients randomized to sodium bicarbonate and 12 (7.5%) to saline (p = 0.79). Renal function did not fully recover in 40.0% and 44.4% of CI-AKI patients, respectively (p = 0.84). No patient required dialysis. Mean costs for preventive hydration and clinical preparation for the contrast procedure were $1158 for sodium bicarbonate vs. $1561 for saline (p < 0.001). Conclusion Short hydration with sodium bicarbonate prior to elective cardiovascular diagnostic or therapeutic contrast procedures is non-inferior to standard periprocedural saline hydration in CKD patients with respect to renal safety and results in considerable healthcare savings. Trial registration Netherlands Trial Register (http://www.trialregister.nl/trialreg/index.asp), Nr NTR2699
ANN Glaucoma Detection using Cup-to-Disk Ratio and Neuroretinal Rim

Glaucoma is a disease in which the intraocular pressure is very high, causing the optic disc to become cupped with eventual everlasting impairment of vision. It is the second leading cause of permanent blindness. It cannot be cured, but its progression can be slowed down by treatment in early stage. Therefore, detecting glaucoma in time is crucial. In this paper glaucoma is classified by extracting two features using retinal fundus images. (i) Cup to Disc Ratio (CDR). (ii) Ratio of Neuroretinal Rim in inferior, superior, temporal and nasal quadrants that is to say ISNT quadrants. Glaucoma frequently damages superior and inferior fibers before temporal and nasal optic nerve fibers and which start decreasing the superior and inferior rims areas and change the order of ISNT rule. Hence, the detection of rim areas in four directions can assist the correct verification of ISNT rule and then improve the correct diagnosis of glaucoma at early stages. In the end, feed forward back propagation neural network is used for classification based on the above two features. The tool used to accomplish the objective is MATLAB R2013a. The average accuracy of the system is around 96%. The method does not rely on trained glaucoma specialists or specialized and costly OCT/HRT machines. Several fundus retinal images containing normal and glaucoma were applied to the proposed method for demonstration.
Health risk assessment of irradiated topaz

Irradiated topaz gemstones are currently processed for color improvement by subjecting clear stones to neutron or high-energy electron irradiations, which leads to activation of trace elements in the stones. Assessment of the risk to consumers required the identification and quantification of the resultant radionuclides and the attendant exposure. Representative stones from Brazil, India, Nigeria, Sri Lanka were irradiated and analyzed for gamma ray and beta particle emissions, using sodium iodide and germanium spectrometers; and Geiger-Muller, plastic and liquid scintillation, autoradiography, and thermoluminescent-dosimetry measurement techniques. Based on these studies and other information derived from published literature, dose and related risk estimates were made for typical user conditions. New criteria and methods for routine assays for acceptable release, based on gross beta and gross photon emissions from the stones, were also developed.
An architecture for interspatial communication

Digital infrastructure in modern urban environments is currently very Internet-centric, and involves transmitting data to physically remote environments. The cost for this is data insecurity, high response latency and unpredictable reliability of services. In this paper, we lay out a software architecture that inverts the current model by building an operating system designed to securely connect physical spaces with extremely low latency, high bandwidth local-area computation capabilities and service discovery. We describe our early prototype design OSMOSE, which is based on unikernels and a distributed store.
A Dose Distribution Study of Uranyl Nitrate in Zebrafish using Liquid Scintillation and Passivated Implanted Planar Silicon Detectors

Alleman, Lee A. M.S., Purdue University, August 2016. A Dose Distribution Study of Uranyl Nitrate in Zebrafish using Liquid Scintillation and Passivated Implanted Planar Silicon Detectors. Major Professor: Linda H. Nie. Standard curves for a Perkin Elmer TriCarb 2800 liquid scintillation detector (LSC) and a Ludlum 3030p Passivated Implanted Planar Silicon detector have been developed and utilized for studying the dose distribution of depleted uranium (DU) within zebrafish. The DU source was crystallized uranyl nitrate (N2O8U•6H2O) solution, normally used for staining in electron microscopy with a manufactured average specific activity of 0.3 uCi/g. Zebrafish ,both larvae and adults, were exposed to three different mass concentrations, dissected, dissolved and counted using an LSC. The counts were compared to the standard curve correlating the measured activity to that of the mass absorbed. It was found that the larvae were more tolerant to the toxicity of the DU by almost a factor of 10 showing survival up to 200 ppm where the adults had zero survival when exposed to concentrations above 20 ppm. The absorbed DU was observed to concentrate more heavily in the skeletal structure and the blood containing organs (liver and heart) when comparing the relative mass concentrations observed in each organ compared to that of the whole fish exposed to the same concentration. The highest absorbed dose rate was found in the skeletal system at 3.5 mGy/d followed by the blood containing organs at 2.2 mGy/d when exposed to 20 ppm DU. It was also noted that the bioconcentration factors (BCF) of the adult zebrafish followed the same trend observed in similar studies. As the mass concentration of DU was lowered, the BCF calculated for fish exposed increased with a BCF of 130.6 found for those exposed to 20 ppm U and a BCF of 774.2 for fish exposed to 2 ppm. This method shows to present a suitable way of
Outcomes Following Removal of Instrumentation After Posterior Spinal Fusion

Background: Although there is good evidence to support the removal of instrumentation for infection following posterior spine fusion, there are few studies that report outcomes following removal for late operative site pain. The purpose of this study was 3-fold: (1) to determine whether removal of instrumentation following posterior spinal fusion resolves preoperative pain, (2) to determine whether indolent infection not detected before removal of instrumentation is related to late operative site pain, and (3) to determine whether curve progression differs when spinal hardware is removed for infection versus late operative site pain. Methods: A retrospective study of consecutive patients aged 10 to 21 years, who underwent removal of instrumentation after posterior spinal fusion over a 10-year-period was conducted. Patient demographics, preoperative and postoperative imaging results, laboratory studies, and operative findings were reviewed. All patients had a minimum 2-year follow-up. Statistical analysis was performed using 2-sample t test, bivariate analysis, and multivariate logistic regression models. Results: Seventy-five patients were included. Indications for removal of spinal instrumentation were pain (57%), infection (28%), hardware failure (8%), and prominent hardware (7%). The mean time from index procedure to hardware removal was 2.8 years. The average loss of curve correction following complete hardware removal was 23.1 degrees. Patients who underwent removal of hardware because of infection had bigger changes in their curves than those without infection (mean, 33.8 degrees vs. 18.8 degrees). Of the 43 patients with pain, only 40% reported relief of their symptoms following removal of hardware. Sixteen of the 43 patients were found to have indolent infection confirmed by positive intraoperative culture results. Conclusions: Patients should be cautioned that hardware removal after posterior spinal fusion may not provide complete pain relief. Furthermore, there is risk for curve progression following removal of instrumentation, particularly in the setting of infection. Back pain may be an indicator of infection, and intraoperative cultures should be taken at the time of implant removal. Level of Evidence: Level IV; retrospective case series.
Characterisation of articular cartilage progenitor cells : Potential use in tissue engineering

Articular cartilage is a resilient and load bearing material that provides diarthrodial joints with excellent friction, lubrication and wear characteristics required for continuous motion. However, articular cartilage has a poor regenerative capacity and its degeneration is a common cause of morbidity in terms of loss of joint function and osteoarthritis, frequently resulting in the need for total knee replacement. Articular cartilage has a distinct zonal architecture with biochemical and cellular variations existing from the surface zone to the deeper calcified layers. Thus, the development of the tissue must be stringently controlled, both spatially and temporally in order for the complex structure to be established. Importantly, the surface zone is believed to be responsible for the appositional growth of articular cartilage during development and this growth is believed to be driven by a population of slow cycling progenitor cells within the surface zone itself. The focus of this thesis is the isolation and characterisation of articular cartilage progenitor cells together with an exploration of the cells capabilities in potential cartilage repair therapies. The cells were identified on the basis of differential adhesion assays and colony forming ability. Subsequent experiments were carried out to show the differential expression of various cell surface markers eg Notch 1 receptors and the role of the onco-foetal form of fibronectin, known as fibronectin-EDA on the modulation of cell behaviour. In terms of the potential of the cells for use in tissue engineering, a promising feature of the cells is the discovery that enriched populations of the cells can undergo extensive expansion in simple monolayer cultures and yet retain their ability to undergo chondrogenic differentiation. This property may enable the use of the cells in commercial cartilage repair and/or tissue engineering strategies.
Development of an ex Vivo Method for Multi-unit Recording of Microbiota-Colonic-Neural Signaling in Real Time

Background and Objectives: Bidirectional signaling between the gastrointestinal tract and the brain is vital for maintaining whole-body homeostasis. Moreover, emerging evidence implicates vagal afferent signaling in the modulation of host physiology by microbes, which are most abundant in the colon. This study aims to optimize and advance dissection and recording techniques to facilitate real-time recordings of afferent neural signals originating in the distal colon. New Protocol: This paper describes a dissection technique, which facilitates extracellular electrophysiological recordings from visceral pelvic, spinal and vagal afferent neurons in response to stimulation of the distal colon. Examples of Application: Focal application of 75 mM KCl to a section of distal colon with exposed submucosal or myenteric nerve cell bodies and sensory nerve endings evoked activity in the superior mesenteric plexus and the vagal nerve. Noradrenaline stimulated nerve activity in the superior mesenteric plexus, whereas application of carbachol stimulated vagal nerve activity. Exposure of an ex vivo section of distal colon with an intact colonic mucosa to peptidoglycan, but not lipopolysaccharide, evoked vagal nerve firing. Discussion: Previous studies have recorded vagal signaling evoked by bacteria in the small intestine. The technical advances of this dissection and recording technique facilitates recording of afferent nerve signals evoked in extrinsic sensory pathways by neuromodulatory reagents applied to the distal colon. Moreover, we have demonstrated vagal afferent activation evoked by bacterial products applied to the distal colonic mucosa. This protocol may contribute to our understanding of functional bowel disorders where gut-brain communication is dysfunctional, and facilitate real-time interrogation of microbiota-gut-brain signaling.
A Drug Delivery System for Administration of Anti–TNF-α Antibody

Purpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy.
Impact of mycobacterial porins on growth and intracellular persistence

Titel, Inhaltsverzeichnis 1 Introduction 1 1.1 Mycobacteria are distinguished by their growth characteristics 1 1.2 The extremely hydrophobic mycobacterial OM is penetrated by porins 3 1.3 Many slow-growing mycobacteria cause severe diseases 4 1.4 Pathogenic rapidly growing mycobacteria 5 1.5 Environmental persistence of mycobacteria 6 1.6 Goals of this study 7 2 Materials and Methods 9 2.1 Strains and growth conditions 9 2.2 Cell lines and culture conditions 10 2.3 Molecular biology techniques 10 2.4 In silico analysis 10 2.5 Isolation of genomic DNA from mycobacteria 11 2.6 Protein preparation and Western blot 11 2.7 M. bovis BCG experiments 12 2.8 RGM experiments 15 2.9 Construction of the suicide plasmid pSSs003 21 3 Results 23 3.1 Heterologous expression of the porin MspA from M. smegmatis in M. bovis BCG affects its in vitro growth and intracellular persistence. 23 3.2 Porins limit the intracellular persistence of M. smegmatis 30 3.3 Characterization of porins from members of the M. fortuitum-group 38 3.4 Construction of the suicide plasmid pSSs003 49 4 Discussion 52 5 Summary 61 6 Zusammenfassung 63 7 References 65 8 Appendix 77 8.1 Abbreviations 77 8.2 Maps of plasmids 78 8.3 Nucleotide sequences 83 8.4 Publications resulted from this study 89 8.5 Acknowledgements 90 8.6 Erklarung 91
Safeguarding Entry into Mitosis: the Antephase Checkpoint

ABSTRACT Maintenance of genomic stability is needed for cells to survive many rounds of division throughout their lifetime. Key to the proper inheritance of intact genome is the tight temporal and spatial coordination of cell cycle events. Moreover, checkpoints are present that function to monitor the proper execution of cell cycle processes. For instance, the DNA damage and spindle assembly checkpoints ensure genomic integrity by delaying cell cycle progression in the presence of DNA or spindle damage, respectively. A checkpoint that has recently been gaining attention is the antephase checkpoint that acts to prevent cells from entering mitosis in response to a range of stress agents. We review here what is known about the pathway that monitors the status of the cells at the brink of entry into mitosis when cells are exposed to insults that threaten the proper inheritance of chromosomes. We highlight issues which are unresolved in terms of our understanding of the antephase checkpoint and provide some perspectives on what lies ahead in the understanding of how the checkpoint functions.
Self-Management of Type 2 Diabetes

The purpose of this study was to explore diabetes self-management strategies and underpinnings of behaviors among Vietnamese with type 2 diabetes. Using Leventhal’s illness representation model, semistructured interviews were conducted with a convenience sample of 23 participants, 14 women and 9 men. NVivo 8 software was used for content analysis. Data revealed that participants constructed implicit theories of the identity, causes, consequences, timeline, and controllability of diabetes, which were inconsistent with the biomedical literature. Participants labeled diabetes by their symptoms of hypo-/hyperglycemia, and they focused on the relief of these symptoms. However, the participants’ focus on symptomatology undermined their use of blood glucose monitoring to manage diabetes as a majority of the participants had diabetes-related complications. Participants integrated the continuum of Eastern and Western treatment belief systems to achieve a balance to create harmony between the two systems.
Systems Pharmacology: A Unified Framework for Prediction of Drug-Target Interactions.

BACKGROUND Drug discovery is one important issue in medicine and pharmacology area. Traditional methods using target-based approach are usually time-consuming and ineffective. Recently, the problems are approached in a system-level view and therefore it is called systems pharmacology. This research field deals with the problems in drug discovery by integrating various kinds of biomedical and pharmacological data and using advanced computational methods. Ultimately, the problems are more effectively solved. One of the most important problem in systems pharmacology is prediction of drug-target interactions. METHODS In this review, we are going to summarize various computational methods for this problem. RESULTS More importantly, we formed a unified framework for the problem. In addition, to study human health and disease in a more systematically and effectively, we also presented an integrated scheme for a wider problem of prediction of disease-gene-drug associations. CONCLUSION By presenting the unified framework and the integrated scheme, underlying computational methods for problems in systems pharmacology can be understood and complex relationships among diseases, genes and drugs can be identified effectively.