Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of somatization disorder and somatization symptoms among primary care patients.

BACKGROUND Diagnostic criteria for somatization disorder emphasize its early onset and long-term stability. Research assessments of somatization disorder depend on lifetime recall of medically unexplained somatic symptoms. METHODS Longitudinal data from the World Health Organization Psychological Problems in General Health Care study were used to examine stability of somatization disorder and somatization symptoms over 12 months. At 15 study sites in 14 countries, consecutive primary care patients (N = 25916) were screened using the 12-item General Health Questionnaire. A stratified random sample (n = 5447) was selected for a baseline diagnostic assessment using the Composite International Diagnostic Interview. All cases and a random sample of noncases were asked to complete a follow-up diagnostic assessment 12 months later (n = 3196). RESULTS While the baseline and 12-month interviews identified a similar number of patients with DSM-IV somatization disorder (74 and 70), only 21 cases were consistently identified at both assessments. Examination of individual symptoms found that 61% of lifetime medically unexplained somatic symptoms detected at baseline were not detected during the lifetime interview 12 months later. When analyses were broadened to all lifetime symptoms reported at baseline (including those found to be "medically explained" or "not clinically significant"), 43% of lifetime symptoms reported at baseline were "lost" 12 months later. CONCLUSIONS Given that the baseline and follow-up assessments both asked about lifetime symptoms, the loss of somatization disorder or individual somatic symptoms can only represent inconsistent recall. The instability of recall observed here has significant implications for the diagnosis of somatization disorder by structured interview and may also have implications for current diagnostic criteria.
Big Data Analytics in Social Streams

Detection of emerging topics are now receiving renewed interest motivated by the rapid growth of s ocial networks. Conventional term-frequency-based approac hes may not be appropriate in this context, because the inf ormation exchanged are not only texts but also images, URLs, and videos. We focus on the social aspects of these networks. T hat is, the links between users that are generated dynamically intentionally or unintentionally through replies, mentions, and retweets. We propose a probability model of the mentioning behav iour of a social network user, and propose to detect the emer gence of a new topic from the anomaly measured through the mod el. We combine the proposed mention anomaly score with a r ecently proposed change-point detection technique based on the Sequentially Discounting Normalized Maximum Likelihood (SDNML), or with Kleinberg’s burst model. Aggregating anomaly scores from hundreds of users, we show that we can detect emerging topics only based on the reply/ment ion relationships in social network posts. We demonstra te our technique in a number of real data sets we gathered from Twitter. The experiments show that the proposed men tion anomaly-based approaches can detect new topics at l east as early as the conventional term-frequency-based approach, and sometimes much earlier when the keyword is ill-defi ned. Keywords-Topic Detection, Anomaly Detection, Social Networks, Sequentially Discounted Maximum Likelihood Coding, Burst detection
Systems biotechnology for protein production in Pichia pastoris

Abstract The methylotrophic yeast Pichia pastoris (syn. Komagataella spp.) is one of the most important production systems for heterologous proteins. After the first genome sequences were published in 2009, tremendous effort was made to establish systems‐level analytical methods. Methylotrophic lifestyle was one of the most thoroughly investigated topics, studied at the levels of transcriptome, proteome and metabolic flux. Also the responses of P. pastoris to environmental stress conditions experienced during high cell density production processes were studied. Metabolomics and flux analysis revealed the plasticity of the cellular metabolism in its adaption to the production of foreign proteins and served as blueprints for subsequent cell engineering and/or process design. The transcriptional response elicited by overexpression of heterologous proteins seems to depend on the nature and complexity of the recombinant product. Based on these data, novel targets for strain engineering could be deduced from transcriptomics and proteomics data mining and effectively enhanced protein secretion. Transcriptional regulation data also served as a valuable resource to identify novel promoters with the desired regulatory characteristics. This review aims to provide a comprehensive overview of systems biology applications in P. pastoris ranging from increased understanding of cell physiology to improving recombinant protein production in this cell factory.
Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.
Therapeutic approaches for refractory germ cell cancer

ABSTRACT Introduction: Most germ cell cancer patients with metastatic disease are cured by cisplatin-based combination chemotherapy. 30% of metastatic patients will develop relapse or progress despite adequate first-line treatment and will require salvage therapy, with about 10% of metastasized patients ultimately developing platinum-resistant and fatal disease. Areas covered: Based on a comprehensive literature search of MEDLINE, EMBASE and conference proceedings of ESMO, ASCO and EAU meetings, this review provides an overview on current and potential future treatment options for platinum-refractory germ cell cancer patients including cytostatics and molecularly targeted therapies. Expert commentary: Treatment of platinum-refractory disease remains challenging and long-term survival is rarely achieved despite multimodal treatment approaches. Targeted treatment approaches do not yet play a role in the treatment of platinum-refractory disease due to lacking efficacy in small, unselected clinical trials. Inclusion of patients into clinical trials is strongly recommended.
Adjacent Segment Degeneration after Single-Level PLIF: Comparison between Spondylolytic Spondylolisthesis, Degenerative Spondylolisthesis and Spinal Stenosis

Study Design A retrospective study. Purpose To comparatively investigated the rate of the adjacent segment degeneration and the clinical outcomes in patients with spondylolytic spondylolisthesis, spinal stenosis or degenerative spondylolisthesis. Overview of Literature There have been few studies reported on the adjacent segment degeneration following posterior lumbar interbody fusion(PLIF). Many risk factors for the adjacent segment degeneration following PLIF have been proposed. The range of decompression has been presented as one of the risk factors, yet controversial. Methods This study enrolled sixty-three patients who had been treated with single-level PLIF and who were followed up for more than two years. The patients were divided into 3 groups based on the preoperative diagnosis. We analyzed the difference between the preoperative and postoperative intervertebral disc heights of the superior adjacent segments. The incidence rates of instability and the clinical outcomes were comparatively analyzed between each group. Results The average age of the patients was 55.8 years in the spondylolytic spondylolisthesis group, 65.9 years in the degenerative spondylolisthesis group and 60.4 years in the spinal stenosis group. The average follow-up period was 44 months, 43 months and 42 months, respectively. At the last follow-up, compared to the preoperative period, the intervertebral disc height decreased in all three groups. A statistically significant decrease (p < 0.01) was observed only in the spondylolytic spondylolisthesis group and no significant difference was observed between each group (p = 0.41). The incidence rate of instability and the clinical outcome were not significantly different between each group. Conclusions Spondylolytic spondylolisthesis with total laminectomy and single-level PLIF showed no significant difference in the superior adjacent segment degeneration and instability, and the clinical outcome as compared to that of partial laminectomy with single-level PLIF for treating degenerative spondylolisthesis or spinal stenosis.
A neural network learning relative distances

Data mining and knowledge discovery aim at the detection of new knowledge in data sets produced by some data generating process. There are (at least) two important problems associated with such data sets: missing values and unknown distributions. This is in particular a problem for clustering algorithms, be it statistical or neuronal. For such purposes a distance metric comparing high dimensional vectors is necessary for all data points. Much handwork is necessary in today's data mining systems to find an appropriate metric. In this work a novel neural network, called ud-net is defined. Ud-nets are able to adapt to unknown distributions of data. The output of the networks may be interpreted as a distance metric. This metric is also defined for data with missing values in some components and the resulting value is comparable to complete data sets. Experiments with known distributions that were distorted by nonlinear transformations show that ud-net produce values on the transformed data that are very comparable to distance measures on the untransformed distributions. Ud-nets are also tested with a data set from a stock picking application. For this example the results of the networks are very similar to results obtained by the application of hand tuned nonlinear transformations to the data set.
B . Renaissance Through Steady Characterization

I. I ntroduction A. D iscovery and Fall B. R enaissance Through Steady Characterization II. R egulatory T Cell Subsets A. N aturally Occurring CD4 Regulatory T cells B. In duced (Adaptive) CD4 Regulatory T Cells C. N aturally Occurring and Induced CD8 Regulatory T Cells III. M echanisms Mediating the Suppressive Function IV. R egulatory T Cells in Cancer A. R egulatory T Cells in Solid Malignancies B. R egulatory T Cells in Hematologic Malignancies C. R egulatory T Cells as Biomarkers V. A ccumulation of Regulatory T cells A. C ompartmental Redistribution B. E xpansion C. D e Novo Generation D. P referential Survival VI. A ntigen Specificity of Tregs in Cancer VII. C ancer Vaccines and Regulatory T Cells VIII. T argeting Regulatory T Cells in Cancer Therapy A. D epletion of Regulatory T Cells B. T argeting Function of Regulatory T Cells C. D isrupting Intratumoral Homing of Regulatory T Cells D. M odulation of Regulatory T Cell Proliferation/Conversion E. T argeting the Antioxidative Capacity of Regulatory T Cells IX. C oncluding Remarks R eferences
Preliminary evaluation of differentiation of benign and malignant breast tumors using non-invasive diagnostic modalities.

Preliminary evaluation of statistical modeling for non-invasive detection of malignancy in the prevalence of breast diseases is discussed. The standard databases for breast cancer symptoms, mammography diagnosing features and breast cancer ultrasound Elastography imaging screening standards were used, with ten dataset features as attributes. The satisfying conditions of the features were categorized for the classification as benign or malignant classes. The interpretation criteria in Elastography consist of the qualitative parameter elasticity score and the quantitative parameter strain ratio. Training of dataset was first done using 180 biopsy cases with 132 benign and 48 malignant results. 95% confidence interval for symptomatic was 1.625 to 4.955; mammographic was 1.506 to 5.494 and ultrasound Elastography imaging was 2.213 to 6.087. The model created was further tested with 210 cases using three machine learning classifiers and results were compared with gold standard biopsy results. Performance characteristics were statistically analyzed. The three classifiers have yielded an accuracy of 95.7%, 84.3% and 91.4% respectively and the statistical models proved its efficiency in differentiating malignant from benign.
Multiparty Quantum Communication Complexity of Triangle Finding

Triangle finding (deciding if a graph contains a triangle or not) is a central problem in quantum query complexity. The quantum communication complexity of this problem, where the edges of the graph are distributed among the players, was considered recently by Ivanyos et al. in the two- party setting. In this paper we consider its k-party quantum communication complexity with k >= 3. Our main result is a ~O(m^(7/12))-qubit protocol, for any constant number of players k, deciding with high probability if a graph with m edges contains a triangle or not. Our approach makes connections between the multiparty quantum communication complexity of triangle finding and the quantum query complexity of graph collision, a well-studied problem in quantum query complexity.
Enhanced Aerobic Glycolysis by S‐Nitrosoglutathione via HIF‐1α Associated GLUT1/Aldolase A Axis in Human Endothelial Cells

S‐nitrosoglutathione (GSNO)‐induced apoptosis is associated with reactive oxygen species and loss of mitochondrial Omi/HtrA2 in human endothelial cells (ECs). But its upstream regulation is still not elucidated. Here, we demonstrate that hypoxia induced factor‐1α (HIF‐1α)‐linked aerobic glycolysis is associated with mitochondrial abnormality by treatment of human EC‐derived EA.hy926 cells with GSNO (500 µM) for 6 h. GSNO exposure increased the levels of Aldolase A and glucose transporter‐1 (GLUT1) mRNAs and proteins. And selectively enhanced aldolase A activity to form glyceraldehyde 3‐phosphate, dihydroxyacetone phosphate, which subsequently increased intracellular levels of methylglyoxal and reactive oxygen species in parallel. Using the biotin switch assay, we found that GSNO increased the S‐nitrosylating levels of total protein and HIF‐1α. Knockdown of HIF‐1α with siRNA attenuated its target aldolase A and GLUT1 expression but not VEGF. In contrast, nitrosylation scanvenger dithiothreitol could decrease all the protein levels. It suggested that aerobic glycolytic flux was more dependent on HIF‐1α level, and that HIF‐1α S‐nitrosylation was crucial for its target expression under the normoxic condition. Moreover, GSNO‐induced PI3 K (phosphoinositide 3‐kinase)/Akt phosphorylation might contribute to HIF‐1α stabilization and nucleus translocation, thereby aiding aldolase A and GLUT1 mRNAs upregulation. Taken together, higher concentration GSNO promotes glycolytic flux enhancement and methylglyoxal formation via HIF‐1α S‐nitrosylation. These findings reveal the mechanism of enhanced glycolysis‐associated mitochondrial dysfunction in ECs by GSNO exposure under normoxic and non‐hyperglycemic condition. And offer the early potential targets for vascular pathophysiological evaluation. J. Cell. Biochem. 118: 2443–2453, 2017. © 2017 Wiley Periodicals, Inc.
Brain-Computer Interfaces: from theory to practice

Brain-Computer Interfaces (BCI) are a new kind of humanmachine interfaces emerging on the horizon. They form a communication pathway between the brain and a machine. This can be achieved by measuring brain signals and translate them directly into control commands. Such a system allows people with severe motor disabilities to manipulate their environment in an alternative way. However there’s still a lot of work to be done to make it usable in daily life. In this contribution we give a tutorial overview of existing methods and possible applications.
Blockade of surface-bound TGF-β on regulatory T cells abrogates suppression of effector T cell function in the tumor microenvironment

Targeting a cytokine on the surface of regulatory T cells inhibits their suppression of tumor cell killing by effector T cells. Blocking immunosuppression The antitumor effects of CD8+ T cells can be blocked in the tumor microenvironment, including through the suppressive function of regulatory T cells (Tregs). Standard in vitro systems fail to recapitulate the conditions that immune cells are exposed to in vivo. Budhu et al. used a three-dimensional, collagen-fibrin gel system to investigate the effects of CD8+ T cells on cocultured melanoma cells excised from mouse tumors. The antitumor activity of the CD8+ T cells was inhibited by the presence of tumor-derived Tregs, which depended on cell-cell contact or close proximity, required the cytokine TGF-β on the Treg cell surface, and resulted in the increased cell surface expression of the immune checkpoint receptor PD-1 on the CD8+ T cells. A blocking antibody against TGF-β prevented immunosuppression, suggesting a therapeutic strategy to inhibit Treg activity in tumors. Regulatory T cells (Tregs) suppress antitumor immunity by inhibiting the killing of tumor cells by antigen-specific CD8+ T cells. To better understand the mechanisms involved, we used ex vivo three-dimensional collagen-fibrin gel cultures of dissociated B16 melanoma tumors. This system recapitulated the in vivo suppression of antimelanoma immunity, rendering the dissociated tumor cells resistant to killing by cocultured activated, antigen-specific T cells. Immunosuppression was not observed when tumors excised from Treg-depleted mice were cultured in this system. Experiments with neutralizing antibodies showed that blocking transforming growth factor–β (TGF-β) also prevented immunosuppression. Immunosuppression depended on cell-cell contact or cellular proximity because soluble factors from the collagen-fibrin gel cultures did not inhibit tumor cell killing by T cells. Moreover, intravital, two-photon microscopy showed that tumor-specific Pmel-1 effector T cells physically interacted with tumor-resident Tregs in mice. Tregs isolated from B16 tumors alone were sufficient to suppress CD8+ T cell–mediated killing, which depended on surface-bound TGF-β on the Tregs. Immunosuppression of CD8+ T cells correlated with a decrease in the abundance of the cytolytic protein granzyme B and an increase in the cell surface amount of the immune checkpoint receptor programmed cell death protein 1 (PD-1). These findings suggest that contact between Tregs and antitumor T cells in the tumor microenvironment inhibits antimelanoma immunity in a TGF-β–dependent manner and highlight potential ways to inhibit intratumoral Tregs therapeutically.
The Role of EUS — Diagnosis and Therapeutic Interventions in Patients with Acute Pancreatitis

diminished the number of complications. We studied 77 patients with sterile non-necrotic pancreatic or peripancreatic collections. Patients were referred for echoendoscopic evaluation after CT scans (75), MRI (29) and ERCP (47). None had a bulging or communication with MPD according to endoscopic pancreatography or MRI. Thus, transpapillary or endoscopic transmural drainage (cystoduodenostomy or cystogastrostomy) was not feasible. All patients had some type of symptom such as persistent abdominal pain or cholestasis. Simple EUS-guided aspiration was indicated in the following situations: patients with PSC without debris or visible wall, parenchymal collection, when the gap between the gastric wall and cyst was greater than 2.0 cm, and for cysts up to 3.0 cm in diameter. Thirty-three underwent EUS-guided aspiration using a 19G needle (Group II) and 44 were treated by transmural EUS-guided drainage and prosthesis placement (Group I). The vast majority of patients was treated (90.6%). A complete cyst aspiration occurred in all cases (100%) and transmural EUS-guided drainage, based on intention to treat, occurred in 83.3%. No complications occurred in group II. In group I occurred 3 complications (4.4%). These results reveal that EUS-guided drainage is possible in most patients with PSC. Those who underwent aspiration showed a high relapse rate. Thus, EUS-guided aspiration is an alternative in cases where EUS-guided transmural drainage is difficult.