jimnoneill/paper-to-field-training huggingface dataset:
P53 is an independent predictor of tumor recurrence and progression after nephrectomy for patients with localized Renal Cell Carcinoma: Implications for surveillance and adjuvant clinical trials

4546 Background: We attempted to determine which clinical and molecular variables can best predict cancer recurrence following nephrectomy for localized Renal Cell Carcinoma(RCC) Methods: From a custom kidney cancer tissue microarray containing tumor specimens from 366 patients, 193 patients who underwent nephrectomy for localized RCC at UCLA between 1989 and 2000 were identified. The array was then analyzed by immunohistochemistry for CAIX, CAXII, Ki67, Gelsolin, p53, EpCAM, pTEN, and Vimentin . The medical records of these patients were then reviewed for clinical data including age, sex, TNM stage, tumor size, nuclear grade, ECOG performance status(ps), recurrence status(both local and metastatic) and, when applicable, time to recurrence. Univariate and multivariate analyses were conducted to determine independent clinical and molecular predictors of tumor recurrences. Optimal cutoff values for significant molecular markers were evaluated. Results: Fifteen percent of the patients recurred following nephrectomy. Univariate analysis demonstrated tumor size, T stage, grade, ECOG ps, Ki67, EpCAM, and p53 to have an impact on recurrence(p<0.05). However, multivariate analysis demonstrated that the only independent predictors were T stage(p=0.018),ECOG(p=0.004), and p53(p=0.003). An optimal cutoff value for p53 mean staining was determined to be 20% of cells. Patients with localized tumors demonstrating mean p53 staining values above and below this cutoff demonstrated recurrence rates of 35.7% and 13.4%, respectively(p=0.018, RR= 3.28). Conclusions: P53 is the only independent molecular predictor of tumor recurrence for patients undergoing treatment for localized RCC, successfully identifying a subset of patients with a significantly higher probability of recurrence that could derive the greatest benefit from more stringent post surgical surveillance and from adjuvant clinical trials. No significant financial relationships to disclose.

Topic: Renal cell carcinoma treatment
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Current Challenges for German Business in the Russian Market

Abstract The reaction of leading German companies in the Russian market after the start of the special military operation on the territory of Ukraine is considered. Companies interested in resolving the situation as soon as possible decided whether to leave the Russian market or not. The author analyzed the decisions of firms in the general context of winding down German business activities after 2014. After the acute phase of the pandemic ended, trade and economic cooperation between Russia and Germany showed a tendency to recover. However, since February 24, 2022, German companies with a small number of exceptions have generally supported anti-Russian sanctions. The conceptual typology of firms’ decisions, i.e., exit, activity compression, stabilization, and continuation of work in a difficult environment, is explored. It is concluded that the long-term trajectory of the real actions of German companies has fundamentally changed. The analysis made it possible to establish that the foundation of pragmatic market relations towards Russia is being eroded in the German foreign economic policy. This explains why German companies declare their willingness to pay. If during the annexation of Crimea to Russia groups of lobbyists for the interests of the German economy fought to maintain contacts, now such efforts are coming to naught.

Topic: Economic Sanctions and International Relations
Subfield: Economics and Econometrics
Field: Economics, Econometrics and Finance
Domain: Social Sciences
Recent advances and perspectives in nucleotide second messenger signaling in bacteria

Abstract Nucleotide second messengers act as intracellular ‘secondary’ signals that represent environmental or cellular cues, i.e. the ‘primary’ signals. As such, they are linking sensory input with regulatory output in all living cells. The amazing physiological versatility, the mechanistic diversity of second messenger synthesis, degradation, and action as well as the high level of integration of second messenger pathways and networks in prokaryotes has only recently become apparent. In these networks, specific second messengers play conserved general roles. Thus, (p)ppGpp coordinates growth and survival in response to nutrient availability and various stresses, while c-di-GMP is the nucleotide signaling molecule to orchestrate bacterial adhesion and multicellularity. c-di-AMP links osmotic balance and metabolism and that it does so even in Archaea may suggest a very early evolutionary origin of second messenger signaling. Many of the enzymes that make or break second messengers show complex sensory domain architectures, which allow multisignal integration. The multiplicity of c-di-GMP-related enzymes in many species has led to the discovery that bacterial cells are even able to use the same freely diffusible second messenger in local signaling pathways that can act in parallel without cross-talking. On the other hand, signaling pathways operating with different nucleotides can intersect in elaborate signaling networks. Apart from the small number of common signaling nucleotides that bacteria use for controlling their cellular “business,” diverse nucleotides were recently found to play very specific roles in phage defense. Furthermore, these systems represent the phylogenetic ancestors of cyclic nucleotide-activated immune signaling in eukaryotes.

Topic: Bacterial Genetics and Biotechnology
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Endoplasmic reticulum stress impedes regulated secretion by governing key exocytotic and granulogenic molecular switches

ABSTRACT Dense core vesicles (DCVs) and synaptic vesicles are specialised secretory vesicles in neurons and neuroendocrine cells, and abnormal release of their cargo is associated with various pathophysiologies. Endoplasmic reticulum (ER) stress and inter-organellar communication are also associated with disease biology. To investigate the functional status of regulated exocytosis arising from the crosstalk of a stressed ER and DCVs, ER stress was modelled in PC12 neuroendocrine cells using thapsigargin. DCV exocytosis was severely compromised in ER-stressed PC12 cells and was reversed to varying magnitudes by ER stress attenuators. Experiments with tunicamycin, an independent ER stressor, yielded similar results. Concurrently, ER stress also caused impaired DCV exocytosis in insulin-secreting INS-1 cells. Molecular analysis revealed blunted SNAP25 expression, potentially attributed to augmented levels of ATF4, an inhibitor of CREB that binds to the CREB-binding site. The effects of loss of function of ATF4 in ER-stressed cells substantiated this attribution. Our studies revealed severe defects in DCV exocytosis in ER-stressed cells for the first time, mediated by reduced levels of key exocytotic and granulogenic switches regulated via the eIF2α (EIF2A)–ATF4 axis.

Topic: Endoplasmic Reticulum Stress and Disease
Subfield: Cell Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology

ACh may set the dynamics of cortical function to those appropriate for learning new information. In models of the putative associative memory function of piriform cortex, selective suppression of intrinsic but not afferent fiber synaptic transmission by ACh prevents recall of previous input from interfering with the learning of new input (Hasselmo, 1993). Selective cholinergic suppression may play a similar role in the hippocampal formation, where Schaffer collateral synapses in stratum radiatum (s. rad) may store associations between activity in region CA3 and the entorhinal cortex input to region CA1 terminating in stratum lacunosum-moleculare (s. l-m). A computational model of region CA1 predicts that for effective associative memory function of the Schaffer collaterals, cholinergic suppression of synaptic transmission should be stronger in s. rad than in s. l-m. In the hippocampal slice preparation, we tested the effect of the cholinergic agonist carbachol (0.01–500 microM) on synaptic transmission in s. rad and s. l-m. Stimulating and recording electrodes were simultaneously placed in both layers, allowing analysis of the effect of carbachol on synaptic potentials in both layers during the same perfusion in each slice. Carbachol produced a significantly stronger suppression of stimulus- evoked EPSPs in s. rad than in s. l-m at all concentrations greater than 1 microM. At 100 microM, EPSP initial slopes were suppressed by 89.1 +/- 3.0% in s. rad, but only by 40.1 +/- 4.1% in s. l-m. The muscarinic antagonist atropine (1 microM) blocked cholinergic suppression in both layers. These data support the hypothesis that synaptic modification of the Schaffer collaterals may store associations between activity in region CA3 and the afferent input to region CA1 from the entorhinal cortex. In simulations, feedback regulation of cholinergic modulation based on activity in region CA1 sets the appropriate dynamics of learning for novel associations, and recall for familiar associations.

Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Post Balloon Stent Right Coronary Artery Aneurysm: Cardiologist's Nightmare

Coronary artery aneurysm is an uncommon complication after balloon angioplasty and stent insertion but not rare. A sixty three years old male presented with acute onset chest pain after 1 year of stent insertion in RCA (Right coronary artery). Investigations revealed RCA aneurysm with stent thrombosis. This was managed successfully by surgical resection of aneurysmal sac and removal of the occluded stent with ligation of RCA followed by distal RCA anastomosis under femoro- femoral bypass during meticulous dissection of the aneurismal sac followed by CABG under cardiopulmonary bypass.

Topic: Kawasaki Disease and Coronary Complications
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
LHD LHDGAUSS_RAY_MWRM3 #156520.1 (analyzed)

Ray trajectories for microwave reflectometry (mwrm) at set3 point obtained using ray-tracing code LHDGauss.

Topic: Genetic and phenotypic traits in livestock
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
INFLUENCE OF THE MATRIX OF AQUEOUS SOLUTIONS ON THE ADSORPTION OF ENDOCRINE DISRUPTORS BY FULLERENE C60

In this work, fullerene (C60) was selected as a model carbon nanomaterial, humic acid (HA) as the model natural organic matter and bisphenol A (BPA), as a moderate hydrophobic organic contaminant. The effects of ionic strength, concentration of organic matter and of the pH over the adsorption of BPA on C60 were studied, as well as the competition between the BPA and the HA at the active sites of the C60. A possible adsorption mechanism was proposed as well as an attempt to study the sorption process in real environmental samples with characteristics alike to the optimum ones found in the synthetic samples studied.

Topic: Fullerene Chemistry and Applications
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Gender differences in repetitive behaviours in children diagnosed with autism spectrum disorder

Repetitive behaviours are one of the main criteria contributing to a diagnosis of autism spectrum disorder (ASD), along with deficits in social communication and interaction. They refer to predictable actions that the child displays repeatedly and/or performs similarly or identically. These actions include a wide range of behaviours such as motor stereotypies, preoccupation with parts of objects, insistence on sameness, limited interests, ritualised behaviours, and sensory hypo- and hyper-reactivity. The prevalence of ASD is steadily increasing, and it is a disorder that has been diagnosed more frequently in boys than girls since its inception. Numerous studies have reported contradictory findings regarding gender differences in the quantity and quality of repetitive behaviours. Therefore, the aim of this study was to investigate whether there are gender differences in repetitive behaviours in children with ASD between the ages of 6 and 9 years, as well as to describe these differences. The participants included 50 parents of children with autism spectrum disorder (30 boys and 20 girls), who were between 6 and 9 years old and had (above) average intellectual abilities. All participants completed the Revised Scale of Repetitive Behaviours and the data obtained were statistically analysed using non-parametric methods. The results indicate that girls exhibit more self-injurious behaviours and less restricted behaviours than boys. No statistically significant gender differences were found for the other subscales of the questionnaire, suggesting that other behaviours occur equally in boys and girls. Overall, repetitive behaviours can be considered as an equally moderate problem for both parents of boys and girls.

Topic: Autism Spectrum Disorder Research
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
An evaluation of the dot-ELISA procedure as a diagnostic test in an area with a high prevalence of human Toxocara canis infection

The aim of this work was to evaluate a dot-enzyme-linked immunosorbent assay (dot-ELISA) using excretory-secretory antigens from the larval stages of Toxocara canis for the diagnosis of toxocariasis. A secondary aim was to establish the optimal conditions for its use in an area with a high prevalence of human T. canis infection. The dot-ELISA test was standardised using different concentrations of the antigen fixed on nitrocellulose paper strips and increasing dilutions of the serum and conjugate. Both the dot-ELISA and standard ELISA methods were tested in parallel with the same batch of sera from controls and from individuals living in the problem area. The best results were obtained with 1.33 µg/mL of antigen, dilutions of 1/80 for the samples and controls and a dilution of 1/5,000 for the anti-human IgG-peroxidase conjugate. All steps of the procedure were performed at room temperature. The coincidence between ELISA and dot-ELISA was 85% and the kappa index was 0.72. The dot-ELISA test described here is rapid, easy to perform and does not require expensive equipment. Thus, this test is suitable for the serological diagnosis of human T. canis infection in field surveys and in the primary health care centres of endemic regions.

Topic: Parasitic Infections and Diagnostics
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Ectopic lymphoid structures in the aged lacrimal glands

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1+ cells and CD19+B220+ cells. B220+CD19+ cells were GL7+ (germinal center-like) and marginal zone-like and progressively increased with age. There was an upregulation of transcripts related to T follicular helper cells, and the number of these cells also increased as mice aged. Compared to a mouse model of Sjögren syndrome, aged LGs have similar transcriptome responses but also unique ones. And lastly, the ectopic lymphoid structures in aged LGs are not exclusive to a specific mouse background as aged diverse outbred mice also have immune infiltration. Altogether, this study identifies a profound change in the immune landscape of aged LGs where B cells become predominant. Further studies are necessary to investigate the specific function of these B cells during the aged LGs.

Topic: Salivary Gland Disorders and Functions
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
The membrane-bound isoform of stem cell factor synergizes with soluble flt3 ligand in supporting early hematopoietic cells in long-term cultures of normal and aplastic anemia bone marrow.

The hematopoietic growth factors stem cell factor (SCF) and flt3 ligand (flt3L) are produced within the hematopoietic microenvironment in a membrane-bound and soluble isoform. To elucidate the relevance of the two isoforms in the network of early-acting cytokines, we examined the interaction of membrane-bound SCF with the soluble forms of SCF and flt3L in long-term cultures of human bone marrow cells. Feeder layers of the murine SCF-deficient Steel stromal cell line transfected with human cDNA stably expressing SCF as a transmembrane molecule were used to support growth of mononuclear cells and CD34+ progenitors derived from normal human bone marrow or from hypoplastic marrow of patients with aplastic anemia (AA). The output of nonadherent progenitor cells representing colony-forming units (CFU) and high-proliferative potential colony-forming cells (HPP-CFC) was scored weekly in secondary methylcellulose cultures; the number of colonies derived from long-term culture-initiating cells (LTC-IC) was determined in nonadherent and adherent cells at 5 weeks. Membrane-bound SCF expressed in the stromal layer was more effective than soluble SCF and soluble flt3L in maintaining clonogenic progenitors. Furthermore, the transmembrane form of SCF effectively synergized with both exogenously supplied factors, although the effect of flt3L was superior to the effect of soluble SCF. In cultures of normal bone marrow cells, addition of flt3L enhanced the total number of CFU and HPP-CFC-type progenitors, primarily of the granulocyte/macrophage lineage, by six- to ninefold after 3 weeks and of LTC-IC-derived colonies by 13-fold after 5 weeks of culture. In cultures of AA cells, both the number and the survival rate of clonogenic precursors were severely impaired even in the presence of flt3L, which, however, yielded a two- to sixfold enhancement of CFU and HPP-CFC numbers at 1 to 2 weeks. In comparison with the hematopoietic function of human Dexter-type stroma cultures, murine feeders expressing high levels of membrane-associated human SCF were equivalent in supporting hematopoiesis during the initial 3 to 4 culture weeks when supplemented with flt3L. These results demonstrate that soluble flt3L interacts with membrane-bound SCF in supporting the long-term growth of bone marrow progenitor cells. The hypothesis that SCF and flt3L function synergistically during the very early stages of human hematopoiesis is thereby reinforced.

Topic: Hematopoietic Stem Cell Transplantation
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
LQG-MP: Optimized path planning for robots with motion uncertainty and imperfect state information

In this paper we present LQG-MP (linear-quadratic Gaussian motion planning), a new approach to robot motion planning that takes into account the sensors and the controller that will be used during the execution of the robot’s path. LQG-MP is based on the linear-quadratic controller with Gaussian models of uncertainty, and explicitly characterizes in advance (i.e. before execution) the a priori probability distributions of the state of the robot along its path. These distributions can be used to assess the quality of the path, for instance by computing the probability of avoiding collisions. Many methods can be used to generate the required ensemble of candidate paths from which the best path is selected; in this paper we report results using rapidly exploring random trees (RRT). We study the performance of LQG-MP with simulation experiments in three scenarios: (A) a kinodynamic car-like robot, (B) multi-robot planning with differential-drive robots, and (C) a 6-DOF serial manipulator. We also present a method that applies Kalman smoothing to make paths C k -continuous and apply LQG-MP to precomputed roadmaps using a variant of Dijkstra’s algorithm to efficiently find high-quality paths.

Topic: Robotic Path Planning Algorithms
Subfield: Computer Vision and Pattern Recognition
Field: Computer Science
Domain: Physical Sciences
Histopathologic and Immunohistochemical Features of Neuroblastoma: A Tool for Evaluating Prognosis

To investigate the relationship of morphologic appearance with other parameters such as age at diagnosis, primary site and clinical stage in regard to the prognosis, we examined a total of 20 neuroblastomas of various sites from children undergoing treatment at the Catholic University of Rome and Regina Elena Cancer Institute of Rome. We used a histopathologic classification, developed by Shimada et al. (JNCI, 1984), based on the presence of Schwann cells and ganglio-neuromatous component, neuroblastic maturation and transition to ganglionic forms, and number of mitotic and karyor-rhetic nuclei. We observed a 100% 2-year survival for patients in the favorable groups (13 patients) and 0% 2-year survival for children (7 patients) in the group with unfavorable histology. Furthermore, immunohistochemical evaluation of neural markers such as NSE, S-100 protein and neurofilaments offered additional important information. Our results confirm that the combination of pathologic, immunohistochemical and clinical criteria can be usefully employed to predict the outcome of neuroblastomas.

Topic: Neuroblastoma Research and Treatments
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
'I'll just take the car': improving bicycle transportation to encourage its use on short trips

Cycling for transport in New Zealand is a minority activity, yet the recreational cycling market is growing. The car is the most popular choice of travel mode by far. There is a clear desire to encourage more cycling in New Zealand, but limited understanding of who will be the next cyclists and how to encourage them. This research, from July 2008 to June 2010, applied the affective design methodology to the goal of increasing cycling in New Zealand. A literature review revealed that overseas best practice is for integrated local cycling policies. Theories of diffusion of innovations and contemplation of change were highlighted and used to inform the project. A review of the New Zealand cycling market showed limited choice of and access to cycling tools. A survey of 234 New Zealand cyclists and non-cyclists demonstrated differences between the groups in perception of bicycles and cyclists, with more agreement for unfamiliar cyclists and bicycles. Practical workshops explored the effect of direct cycling experience on perceptions. A practical cycling system design model was proposed, along with recommendations for its implementation.

Topic: Urban Transport and Accessibility
Subfield: Transportation
Field: Social Sciences
Domain: Social Sciences