Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimally invasive local therapies for liver cancer

Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.
Functional Genomics of Sleep and Circadian Rhythm Invited Review: How sleep deprivation affects gene expression in the brain: a review of recent findings

Cirelli, Chiara. Invited Review: How sleep deprivation affects gene expression in the brain: a review of recent findings. J Appl Physiol 92: 394‐400, 2002. —The identification of the molecular correlates of sleep and wakefulness is essential to understand the restorative processes occurring during sleep, the cellular mechanisms underlying sleep regulation, and the functional consequences of sleep loss. To determine what molecular changes occur in the brain during the sleep-waking cycle and after sleep deprivation, our laboratory is performing a systematic screening of brain gene expression in rats that have been either sleeping or spontaneously awake for a few hours and in rats that have been sleep deprived for different periods of time ranging from a few hours to several days. So far, ;10,000 transcripts expressed in the cerebral cortex have been screened. The expression of the vast majority of these genes does not change either across behavioral states or after sleep deprivation, even when forced wakefulness is prolonged for several days. A few hours of wakefulness, either spontaneous or forced by sleep deprivation, increase the expression of the same small groups of genes: immediate-early genes/transcription factors, genes related to energy metabolism, growth factors/adhesion molecules, chaperones/heat shock proteins, vesicle- and synapse-related genes, neurotransmitter/hormone receptors, neurotransmitter transporters, and enzymes. Sleep, on the other hand, induces the expression of a few unknown transcripts whose characterization is in progress. Thus, although the characterization of the molecular correlates of behavioral states is not yet complete, it is already apparent that the transition from sleep to waking can affect basic cellular functions such as RNA and protein synthesis, neural plasticity, neurotransmission, and metabolism. The pattern of changes in gene expression after long periods of sleep deprivation is unique and does not resemble that of shortterm sleep deprivation or spontaneous wakefulness. A notable exception is represented, however, by the enzyme arylsulfotransferase, whose induction appears to be proportional to the duration of previous wakefulness. Arylsulfotransferase in rodents plays a major role in the catabolism of catecholamines, suggesting that an important role for sleep may be that of interrupting the continuous activity, during wakefulness, of brain catecholaminergic systems. arylsulfotransferase; cerebral cortex; mRNA; sleep; wakefulness
Radiographic Changes in the First Metatarsal Head after Distal Chevron Osteotomy Combined with Lateral Release Through a Plantar Approach

The purpose of this study was to evaluate the development of clinically significant avascular necrosis of the head of the first metatarsal after: (1) distal metatarsal osteotomy of the chevron configuration beginning apically at the center of the metatarsal head and extending into the head metatarsal neck junction and (2) release of the adductor hallucis muscle, the lateral capsulosesamoid ligament, and the lateral head of the flexor hallucis brevis via fibular sesamoidectomy in the majority of procedures (71/77). Although there were initial radiographic findings suspicious of avascular necrosis, subchondral lucencies (28 feet), mottling (40 feet), and focal lucencies (29 feet) in 76% of the feet, at final follow-up (12–43 months, average 25 months) this figure had fallen to 25%. The range of motion of the first metatarsophalangeal joint and articular symptoms were important in this study because of the assumption that these two parameters of evaluation would correspond to the severity of radiographic evidence of avascular necrosis. Only those patients (8 feet) with persistent mottling at final follow-up had a statistically significant decrease in the average range of motion (P = .013), with 51° total arc of motion compared with 64° total arc of motion for the remainder. There were no patients with persistent radiographic changes suggesting avascular necrosis who complained of pain. We concluded from the radiographic and clinical data that if the primary blood supply to the capsule and head of the metatarsal (the first dorsal intermetatarsal artery) is preserved, an extensive lateral release combined with a distal metatarsal osteotomy of the chevron configuration are unlikely to cause clinically significant avascular necrosis of the first metatarsal head. By clinically significant, we refer to range of motion and articular pain.
Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.

Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.
Use of Subtractive Hybridization To Design Habitat-Based Oligonucleotide Probes for Investigation of Natural Bacterial Communities

ABSTRACT We describe a rapid oligonucleotide probe design strategy based on subtractive hybridization which yields probes for 16S rRNA or rRNA genes of individual members of microbial communities that are specific within the context of those communities. This strategy circumvents the need to sequence many similar or identical clones of dominant members of a community. Radioactively labeled subfragments of a cloned 16S rRNA gene sequence for which a probe is required (target) were hybridized with biotinylated total 16S ribosomal DNA (rDNA) amplified from the microbial community, and the hybrids formed were subsequently discarded. The remaining enriched fragments were used to screen a library consisting of cloned subfragments of the target sequence by colony hybridization in order to identify the variable regions of the 16S rRNA gene with the required specificity. The sequencing of random clones in one 16S rDNA library demonstrated that only those clones with 100% sequence identity with the probe fragment were detected by it. Moreover, sequencing of other, randomly selected, probe-positive clones revealed 100% sequence identity with the probe. Probes developed in this way tended to correspond to more variable regions of the 16S rRNA if the target sequences were similar to the sequences of other clones in the library and to less variable regions if the target sequences were phylogenetically isolated within the clone library. Although the absolute specificity of the latter probes, as assessed by comparison with available database sequences, was lower than the absolute specificity of the probes from the more variable regions, they were specific within the context of the environmental samples from which they were derived.
Evaluation of a professional development course for pharmacists on laboratory values: can practice change?

Objectives The practice environment in Alberta has emerged as the most unique in North America, including access to laboratory values, a province‐wide electronic health record and legislation to support additional prescribing authority for qualified pharmacists. A course to help pharmacists integrate laboratory values in their medication management of patients was introduced to prepare pharmacists for these changes. The purpose of this study was to evaluate pharmacists' experience with a continuing professional development (CPD) course and its impact on pharmacists' knowledge, confidence and change in practice.
RNA Microarray Analysis of Macroscopically Normal Articular Cartilage from Knees Undergoing Partial Medial Meniscectomy: Potential Prediction of the Risk for Developing Osteoarthritis

Objectives (i) To provide baseline knowledge of gene expression in macroscopically normal articular cartilage, (ii) to test the hypothesis that age, body-mass-index (BMI), and sex are associated with cartilage RNA transcriptome, and (iii) to predict individuals at potential risk for developing “pre-osteoarthritis” (OA) based on screening of genetic risk-alleles associated with OA and gene transcripts differentially expressed between normal and OA cartilage. Design Healthy-appearing cartilage was obtained from the medial femoral notch of 12 knees with a meniscus tear undergoing arthroscopic partial meniscectomy. Cartilage had no radiographic, magnetic-resonance-imaging or arthroscopic evidence for degeneration. RNA was subjected to Affymetrix microarrays followed by validation of selected transcripts by microfluidic digital polymerase-chain-reaction. The underlying biological processes were explored computationally. Transcriptome-wide gene expression was probed for association with known OA genetic risk-alleles assembled from published literature and for comparison with gene transcripts differentially expressed between healthy and OA cartilage from other studies. Results We generated a list of 27,641 gene transcripts in healthy cartilage. Several gene transcripts representing numerous biological processes were correlated with age and BMI and differentially expressed by sex. Based on disease-specific Ingenuity Pathways Analysis, gene transcripts associated with aging were enriched for bone/cartilage disease while the gene expression profile associated with BMI was enriched for growth-plate calcification and OA. When segregated by genetic risk-alleles, two clusters of study patients emerged, one cluster containing transcripts predicted by risk studies. When segregated by OA-associated gene transcripts, three clusters of study patients emerged, one of which is remarkably similar to gene expression pattern in OA. Conclusions Our study provides a list of gene transcripts in healthy-appearing cartilage. Preliminary analysis into groupings based on OA risk-alleles and OA-associated gene transcripts reveals a subset of patients expressing OA transcripts. Prospective studies in larger cohorts are needed to assess whether these patterns are predictive for OA.
LiveRank: How to Refresh Old Datasets

ABSTRACT This article considers the problem of refreshing a dataset. More precisely, given a collection of nodes gathered at some time (webpages, users from an online social network) along with some structure (hyperlinks, social relationships), we want to identify a significant fraction of the nodes that still exist at present time. The liveness of an old node can be tested through an online query at present time. We call LiveRank a ranking of the old pages so that active nodes are more likely to appear first. The quality of a LiveRank is measured by the number of queries necessary to identify a given fraction of the active nodes when using the LiveRank order. We study different scenarios from a static setting where the LiveRank is computed before any query is made, to dynamic settings where the LiveRank can be updated as queries are processed. Our results show that building on the PageRank can lead to efficient LiveRanks, for web graphs as well as for online social networks.
The metabolism of orally administered l‐DOPA in Parkinsonism

1 . Gas‐liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of l‐DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism. 2 . The output of these compounds was normal before treatment. During drug therapy, large quantities of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were excreted but traces only of 4‐hydroxy‐3‐methoxyphenylethanol. Noradrenaline metabolites showed little change in output other than a small increase in 4‐hydroxy‐3‐methoxymandelic acid. 3 . Information was obtained about a number of minor routes of degradation which might be implicated in the therapeutic action of l‐DOPA. A raised output of m‐hydroxyphenylacetic acid pointed to p‐dehydroxylation of dihydroxyphenylacetic acid by gut flora. Evidence of transamination as a minor metabolic pathway was obtained by finding appreciable urinary levels of 4‐hydroxy‐3‐methoxyphenyllactic acid. A keto‐acid precursor of this compound may act as competitive inhibitor of an enzyme active in the normal degradation route of tyrosine, p‐hydroxyphenylpyruvic acid oxidase, for increased amounts of p‐hydroxyphenyllactic acid, the major metabolic derivative of p‐hydroxyphenylpyruvic acid, accumulated in the urine during DOPA treatment.
Infrared Video Pupillography Coupled with Smart Phone LED for Measurement of Pupillary Light Reflex

Clinical assessment of pupil appearance and pupillary light reflex (PLR) may inform us the integrity of the autonomic nervous system (ANS). Current clinical pupil assessment is limited to qualitative examination, and relies on clinical judgment. Infrared (IR) video pupillography combined with image processing software offer the possibility of recording quantitative parameters. In this study we describe an IR video pupillography set-up intended for human and animal testing. As part of the validation, resting pupil diameter was measured in human subjects using the NeurOptics™ (Irvine, CA, USA) pupillometer, to compare against that measured by our IR video pupillography set–up, and PLR was assessed in guinea pigs. The set-up consisted of a smart phone with a light emitting diode (LED) strobe light (0.2 s light ON, 5 s light OFF cycles) as the stimulus and an IR camera to record pupil kinetics. The consensual response was recorded, and the video recording was processed using a custom MATLAB program. The parameters assessed were resting pupil diameter (D1), constriction velocity (CV), percentage constriction ratio, re-dilation velocity (DV) and percentage re-dilation ratio. We report that the IR video pupillography set-up provided comparable results as the NeurOptics™ pupillometer in human subjects, and was able to detect larger resting pupil size in juvenile male guinea pigs compared to juvenile female guinea pigs. At juvenile age, male guinea pigs also had stronger pupil kinetics for both pupil constriction and dilation. Furthermore, our IR video pupillography set-up was able to detect an age-specific increase in pupil diameter (female guinea pigs only) and reduction in CV (male and female guinea pigs) as animals developed from juvenile (3 months) to adult age (7 months). This technique demonstrated accurate and quantitative assessment of pupil parameters, and may provide the foundation for further development of an integrated system useful for clinical applications.
Analysis of Tribological Performance of a Piston Ring Pack

Performance analysis of a piston ring pack is presented in this investigation with the objective of studying the behavior and interrelationships of key engine parameters such as oil consumption, blow-by/blow-back, power loss and wear loads for typical operating conditions. The analysis is based on an integrated methodology addressing the various physical phenomena associated with ring packs including (a) ring dynamics for axial and twist motions within the grooves to determine flow paths for gases, (b) inter-ring gas dynamics for blow-by and blow-back behavior, (c) mixed lubrication at the ring face-liner conjunction for friction considerations and radial ring dynamics, and (d) oil transport for distribution of lubricant along the liner. Relevant output from each of these phenomenological models such as instantaneous values of (i) inter-ring flow areas, (ii) gas blow-back, (Hi) volume of oil within inter-ring regions, (iv) oil accumulation at top ring's leading edge and (v) liner oil film distribution are utilized by the oil consumption models which enable the calculations from the various consumption mechanisms (due to throw-off, entrainment and evaporation). Additionally, wear loads on the ring faces and liner are calculated based on contact pressures due to mixed lubrication at the ring face-liner interface. Included in this investigation are results from a series of studies undertaken to analyze the behavior of the aforementioned engine parameters over a range of speed and load conditions. Presented as a Society of Tribologists and Lubrication Engineers Paper at the STLE/ASME Tribology Conference in Orlando, Florida, October 11–13, 1999
Identification of γ-Synuclein as a Stage-Specific Marker in Bladder Cancer by Immunohistochemistry

Background Previous studies have shown that the expression level of γ-synuclein (SNCG) is associated with progression of many different malignant tumors. In this study, we discuss and assess the prognostic ability of SNCG in bladder cancer. Material/Methods Medical records (2005–2013) were retrospectively reviewed for the population of interest. SNCG expression was identified immunohistochemically from bladder cancer tissues of 113 bladder cancer patients. The survival rate was calculated by the Kaplan-Meier method. Cox proportional hazard regression model was used for analysis of predictors of bladder cancer. Results SNCG was overexpressed in bladder cancer tissues compared with the normal bladder tissues (p<0.0001). SNCG expression in bladder cancer tissue was strongly related to tumor stage. However, SNCG level was not a prognostic factor of survival. Conclusions Our results demonstrate that SNCG is highly expressed in bladder cancer tissue and its expression is stage-specific, but it is not helpful for predicting outcome in bladder cancer patients.
Morphology and structure of lipoproteins revealed by an optimized negative-staining protocol of electron microscopy

Plasma lipoprotein levels are predictors of risk for coronary artery disease. Lipoprotein structure-function relationships provide important clues that help identify the role of lipoproteins in cardiovascular disease. The compositional and conformational heterogeneity of lipoproteins are major barriers to the identification of their structures, as discovered using traditional approaches. Although electron microscopy (EM) is an alternative approach, conventional negative staining (NS) produces rouleau artifacts. In a previous study of apolipoprotein (apo)E4-containing reconstituted HDL (rHDL) particles, we optimized the NS method in a way that eliminated rouleaux. Here we report that phosphotungstic acid at high buffer salt concentrations plays a key role in rouleau formation. We also validate our protocol for analyzing the major plasma lipoprotein classes HDL, LDL, IDL, and VLDL, as well as homogeneously prepared apoA-I-containing rHDL. High-contrast EM images revealed morphology and detailed structures of lipoproteins, especially apoA-I-containing rHDL, that are amenable to three-dimensional reconstruction by single-particle analysis and electron tomography.
Use of dose modification schedules is effective for blinding trials of warfarin: evidence from the WASID study

Background Randomized clinical trials are blinded to prevent knowledge of treatment assignment from influencing outcomes and their assessments, thus protecting the trial's scientific integrity. Trials involving a warfarin treatment arm are difficult to blind due to the need to continuously adjust dose. Purpose We sought to examine the effectiveness of blinding secondary stroke prevention trials with a warfarin treatment arm in which the blinding system incorporates use of placebo warfarin dose modification schedules for patients in the placebo warfarin arm. Methods We examined treatment assignment guesses of 569 patients or their next of kin as well as study coordinators and principal neurologists at the clinical sites in a multicenter, randomized, double-dummy, double-blinded clinical trial of warfarin and aspirin using dose adjustment schedules for management of placebo warfarin. Results Overall, the crude rates of correct responses are 60% for patient/proxy, 66% for study coordinator, and 56% for principal neurologist. Several indices were used to assess the consistency of guesses with what would be expected if the guessing were done completely at random, and all measures indicate adequate blinding. Limitations Comparison to other trials using warfarin is difficult due to limited data and differences in assessment of blinding. However, results compared favorably to one existing trial. Conclusions Placebo warfarin dose adjustment schedules can protect blinding adequately in trials involving warfarin. Clinical Trials 2008; 5: 23—30. http://ctj.sagepub. com
In vivo and in vitro activities of the gp130-stimulating designer cytokine Hyper-IL-6.

IL-6 is a multifactorial cytokine mediating acute inflammatory responses in the liver. When IL-6 binds to a specific receptor (IL-6R), the IL-6/IL-6R complex associates with the signal transducer gp130, initiating intracellular signaling. A soluble form of the IL-6R (sIL-6R) renders target cells sensitive to IL-6 that do not express the IL-6R on their surfaces. A designer cytokine, termed Hyper-IL-6, consisting of IL-6 covalently linked to the sIL-6R was fully active on gp130-expressing cells at 100- to 1000-fold lower concentrations than unlinked IL-6 and IL-6R. Mice were injected i.p. with Hyper-IL-6 or IL-6. Upon injection of Hyper-IL-6 into mice, the acute phase response, as measured by haptoglobin mRNA expression in the liver, was markedly increased and lasted significantly longer compared with that in mice injected with a 10-fold higher dose of IL-6 alone. On human hepatoma cells, Hyper-IL-6 caused similar effects, indicating that the longer lasting response to the fusion protein could not only be explained by the longer plasma half-life of the fusion protein. Experiments using iodinated IL-6 and Hyper-IL-6 revealed that Hyper-IL-6 bound with high affinity to gp130 and was less efficiently internalized. This effect might explain the longer lasting activity of this protein on cells. The highly active IL-6/sIL-6R designer protein might be of significant clinical importance for the stimulation of cells that are more responsive to the IL-6/sIL-6R complex than to IL-6 alone. Such cells include hemopoietic progenitor cells and hepatocytes.