Miracle-dz/UniFAR-FTUs huggingface dataset:
Robotic radical prostatectomy in patients with high-risk disease: a review of short-term outcomes from a high-volume center.

PURPOSE Patients with high-risk prostate cancer have historically been treated with multimodal therapy and considered poor candidates for minimally invasive surgery. We reviewed our experiences with robot-assisted radical prostatectomy (RARP) in patients with high-risk clinical features. MATERIALS AND METHODS Clinical database review identified high-risk patients undergoing RARP by two high-volume robotic surgeons. D'Amico's criteria for high-risk prostate cancer were utilized: prostate-specific antigen ≥ 20 ng/mL, clinical stage ≥ T2c, or preoperative Gleason grade ≥ 8. About 148 patients were identified in the study group. Mean age at surgery was 60.9 years, and mean body mass index was 27.9. Mean estimated blood loss was 150 cc and the transfusion rate was 2.7%. Median hospital stay was 1 day and the rate of major complications (Clavien grade ≥ 3) was 3.4%. RESULTS Bilateral nerve preservation was feasible in 28.4%, and the rate of positive surgical margins was 20.9%. Final pathology demonstrated extra-capsular disease in 54.1% of patients and 12.3% had lymph node involvement. At 2 years of follow-up, 21.3% of patients had experienced biochemical recurrence or had persistent disease after treatment. Continence was 91.2% (1 pad or less) and total impotence (inability to masturbate) was 48.3%. CONCLUSIONS RARP does not compromise oncologic or functional outcomes in patients with high-risk prostate cancer. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy at experienced centers.
Reducing Physical Restraint Use in Alcohol Withdrawal Patients: A Literature Review

Alcohol withdrawal patients experience symptoms ranging from mild anxiety and disorientation to severe agitation and hallucinations. The most critical of these patients are treated in intensive care units. Physical restraints are often required to maintain patient safety until symptoms resolve. The use of physical restraints is contradictory to nursing values and is unsupported by evidenced-based literature. A literature review was conducted to see what, if any, alternatives have been tested to improve patient care for this complicated patient population.
Oxidative Stress Responses and NRF2 in Human Leukaemia

Oxidative stress as a result of elevated levels of reactive oxygen species (ROS) has been observed in almost all cancers, including leukaemia, where they contribute to disease development and progression. However, cancer cells also express increased levels of antioxidant proteins which detoxify ROS. This includes glutathione, the major antioxidant in human cells, which has recently been identified to have dysregulated metabolism in human leukaemia. This suggests that critical balance of intracellular ROS levels is required for cancer cell function, growth, and survival. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor plays a dual role in cancer. Primarily, NRF2 is a transcription factor functioning to protect nonmalignant cells from malignant transformation and oxidative stress through transcriptional activation of detoxifying and antioxidant enzymes. However, once malignant transformation has occurred within a cell, NRF2 functions to protect the tumour from oxidative stress and chemotherapy-induced cytotoxicity. Moreover, inhibition of the NRF2 oxidative stress pathway in leukaemia cells renders them more sensitive to cytotoxic chemotherapy. Our improved understanding of NRF2 biology in human leukaemia may permit mechanisms by which we could potentially improve future cancer therapies. This review highlights the mechanisms by which leukaemic cells exploit the NRF2/ROS response to promote their growth and survival.
Analysis of delay-induced basal ganglia oscillations: the role of external excitatory nuclei

Basal ganglia are interconnected deep brain structures involved in movement generation. Their persistent beta-band oscillations (13–30 Hz) are known to be linked to Parkinson’s disease motor symptoms. In this paper, we provide conditions under which these oscillations may occur, by explicitly considering the role of the pedunculopontine nucleus (PPN). We analyse the existence of equilibria in the associated firing-rate dynamics and study their stability by relying on a delayed multiple-input/multiple-output (MIMO) frequency analysis. Our analysis suggests that the PPN has an influence on the generation of pathological beta-band oscillations. These results are illustrated by simulations that confirm numerically the analytic predictions of our two main theorems.
Serological Evaluation of Thin-Layer Immunoassay–Enzyme-Linked Immunosorbent Assay for Antibody Detection in Human Trichinellosis

ABSTRACT A new immunoenzymatic test, named the thin-layer immunoassay–enzyme-linked immunosorbent assay (TIA-ELISA), was evaluated for antibody detection in human trichinellosis using excretion and secretion products prepared from Trichinella spiralis muscle larvae. Serum samples from people with positive muscle biopsies or symptoms compatible with the disease (n = 8 or 26, respectively), all reactive in enzyme-linked immunoelectrotransfer blot assay (EITB), as well as 67 serum samples from healthy, EITB-negative people, were tested in an ELISA and TIA-ELISA. TIA-ELISA was performed in polystyrene plastic petri dishes by adding dots of 10 μl each of antigen (7 μg/ml) followed by adding diluted serum and the conjugate. Finally, the substrate mixed with agar was added to develop the reaction. Enzymatic by-products were easily detected by the naked eye as defined dots. Sensitivity and specificity were 76 and 94% for ELISA, and both parameters were 91% for TIA-ELISA. The kappa correlation indices for both tests in relation to EITB were 0.73 and 0.80, respectively. The TIA-ELISA can be carried out with common laboratory equipment in 3 h and uses lower quantities of antigen than EITB and ELISA. Since TIA-ELISA is easy to perform, cheap, sensitive, and specific, the test could be an acceptable alternative to use in clinical laboratories lacking specialized equipment needed for ELISA and EITB and in field studies for antibody detection in human trichinellosis.
Evolutionary computation for biclustering of gene expression

Microarray data are widely used in genomic research due to the enormous potential in gene expression profiling, facilitating the prognosis and the discovering of subtypes of diseases. The gene expression data are organized in matrices, where rows represent genes and columns represent experimental conditions. Each element in the matrix refers to the expression level of a particular gene under a specific condition. Biclustering of gene expression was first proposed by Cheng and Church [2], where the residue of an element in the bicluster and the mean squared residue of a submatrix were introduced. In addition, they adjusted that measure to reject trivial biclusters by means of the row variance. For details about these measures, we refer the reader to [2]. In this work, we address the biclustering problem with evolutionary computation (EC), which has been proven to have an excellent performance on highly complex optimization problems. In this paper we follow the model of biclustering proposed by [2]. As the algorithm, called SEBI, partially uses the squared mean residue, the results have been compared to those of Cheng and Church. In expression data analysis, the most important goal may not be finding the maximum bicluster or even finding a bicluster cover for the data matrix. It is more interesting to find a set of genes showing strikingly similar up–regulation and down– regulation under a set of conditions. A low mean squared residue score plus a large variation from the constant may be a good criterion for identifying these genes and conditions. Therefore, our goal is to find biclusters of maximum size, with mean squared residue lower than a given δ, with a relatively high row variance, and with a low level of overlapping among biclusters.
Human germinal center-associated lymphoma protein expression is associated with improved failure-free survival in Brazilian patients with classical Hodgkin lymphoma

The human germinal center-associated lymphoma (HGAL) gene has prognostic value in diffuse large B-cell lymphoma, and expression of its cognate protein is germinal center-specific. A previous study had suggested that HGAL protein expression might also be related to the outcome in patients with Hodgkin lymphoma (HL). The aim of this study was to confirm the prognostic impact of HGAL protein expression in an independent, well-characterized cohort of 232 patients with classic HL treated uniformly with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Tissue microarray analysis showed HGAL staining in 188 specimens (81%). Failure-free survival (FFS) was superior in patients with early-stage disease, low-risk IPS, and HGAL-positive patients. The estimated 5-year FFS for HGAL-positive and HGAL-negative patients was 82% and 67%, respectively (p = 0.03). In the multivariate analysis, advanced stage and absence of HGAL staining were independent predictors of a worse FFS. This study confirms and validates recent findings of a correlation between HGAL expression and outcome in classical HL.
Partiality and Games: Propositional Logic

We study partiality in propositional logics containing formulas with either undefined or over-defined truth-values. Undefined values are created by adding a four-place connective W termed transjunction to complete models which, together with the usual Boolean connectives is shown to be functionally complete for all partial functions. Transjunction is seen to be motivated from a game-theoretic perspective, emerging from a two-stage extensive form semantic game of imperfect information between two players. This game-theoretic approach yields an interpretation where partiality is generated as a property of non-determinacy of games. Over-defined values are produced by adding a weak, contradictory negation or, alternatively, by relaxing the assumption that games are strictly competitive. In general, particular forms of extensive imperfect information games give rise to a generalised propositional logic where various forms of informational dependencies and independencies of connectives can be studied.
Modeling He-rich subdwarfs through the hot-flasher scenario

We present 1D numerical simulations aimed at studying the hot-flasher scenario for the formation of He-rich subdwarf stars. Sequences were calculated for a wide range of metallicities and physical assumptions, such as the stellar mass at the moment of the helium core flash. This allows us to study the two previously proposed flavors of the hot-flasher scenario (“deep” and “shallow” mixing cases) and to identify a third transition type. Our sequences are calculated by solving simultaneously the mixing and burning equations within a diffusive convection picture, and in the context of standard mixing length theory. We are able to follow chemical evolution during deep-mixing events in which hydrogen is burned violently, and therefore able to present a homogeneous set of abundances for different metallicities and varieties of hot-flashers. We extend the scope of our work by analyzing the effects of non-standard assumptions, such as the effect of chemical gradients, extra-mixing at convective boundaries, possible reduction in convective velocities, or the interplay between difussion and mass loss. Particular emphasis is placed on the predicted surface properties of the models. We find that the hot-flasher scenario is a viable explanation for the formation and surface properties of He-sdO stars. Our results also show that, during the early He-core burning stage, element diffusion may produce the transformation of (post hot-flasher) He-rich atmospheres into He-deficient ones. If this is so, then we find that He-sdO stars should be the progenitors of some of the hottest sdB stars.
Molecular evolution of affinity and flexibility in the immune system

The immune system responds to the introduction of foreign antigens by rapidly evolving antibodies with increasing affinity for the antigen (i.e., maturation). To investigate the factors that control this process at the molecular level, we have assessed the changes in flexibility that accompany ligand binding at four stages of maturation in the 4-4-20 antibody. Our studies, based on molecular dynamics, indicate that increased affinity for the target ligand is associated with a decreased entropic cost to binding. The entropy of binding is unfavorable, opposing favorable enthalpic contributions that arise during complex formation. Computed binding free energies for the various antibody–ligand complexes qualitatively reproduce the trends observed in the experimentally derived values, although the absolute magnitude of free-energy differences is overestimated. Our results support the existence of a correlation between high-affinity interactions and decreased protein flexibility in this series of antibody molecules. This observation is likely to be a general feature of molecular association processes and key to the molecular evolution of antibody responses.
Random Dynamical Systems for Stochastic Evolution Equations Driven by Multiplicative Fractional Brownian Noise with Hurst Parameters H ∈ (1/3, 1/2]

We consider the stochastic evolution equation $du=Audt+G(u)d\omega,\quad u(0)=u_0$ in a separable Hilbert space $V$. Here $G$ is supposed to be three times Frechet-differentiable and $\omega$ is a trace class fractional Brownian motion with Hurst parameter $H\in (1/3,1/2]$. We prove the existence of a unique pathwise global solution, and, since the considered stochastic integral does not produce exceptional sets, we are able to show that the above equation generates a random dynamical system.
Cancer metabolism, stemness and tumor recurrence

Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67−/TOMM20−/COX−/MCT1−); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67−/TOMM20−/COX−/MCT1−). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target “three-compartment tumor metabolism” in head and neck cancers. It is remarkable that two “non-proliferating” populations of cells (Ki-67−/MCT4+) within the tumor can actually determine clinical outcome, likely by providing high-energy mitochondrial “fuels” for proliferative cancer cells to burn. Finally, we also show that in normal mucosal tissue, the basal epithelial “stem cell” layer is hyper-proliferative (Ki-67+), mitochondrial-rich (TOMM20+/COX+) and is metabolically programmed to use mitochondrial fuels (MCT1+), such as ketone bodies and L-lactate. Thus, oxidative mitochondrial metabolism (OXPHOS) is a common feature of both (1) normal stem cells and (2) proliferating cancer cells. As such, we should consider metabolically treating cancer patients with mitochondrial inhibitors (such as Metformin), and/or with a combination of MCT1 and MCT4 inhibitors, to target “metabolic symbiosis. ”
Content modeling for social media text

This thesis focuses on machine learning methods for extracting information from usergenerated content. Instances of this data such as product and restaurant reviews have become increasingly valuable and influential in daily decision making. In this work, I consider a range of extraction tasks such as sentiment analysis and aspect-based review aggregation. These tasks have been well studied in the context of newswire documents, but the informal and colloquial nature of social media poses significant new challenges. The key idea behind our approach is to automatically induce the content structure of individual documents given a large, noisy collection of user-generated content. This structure enables us to model the connection between individual documents and effectively aggregate their content. The models I propose demonstrate that content structure can be utilized at both document and phrase level to aid in standard text analysis tasks. At the document level, I capture this idea by joining the original task features with global contextual information. The coupling of the content model and the task-specific model allows the two components to mutually influence each other during learning. At the phrase level, I utilize a generative Bayesian topic model where a set of properties and corresponding attribute tendencies are represented as hidden variables. The model explains how the observed text arises from the latent variables, thereby connecting text fragments with corresponding properties and attributes. Thesis Supervisor: Regina Barzilay Title: Associate Professor, Electrical Engineering and Computer Science
Modulated waves in a periodically driven annular cavity

Time-periodic flows with spatio-temporal symmetry Z2 × O(2) – invariance in the spanwise direction generating the O(2) symmetry group and a half-period-reflection symmetry in the streamwise direction generating a spatio-temporal Z2 symmetry group – are of interest largely because this is the symmetry group of periodic laminar two-dimensional wakes of symmetric bodies. Such flows are the base states for various three-dimensional instabilities; the periodically shedding two-dimensional circular cylinder wake with three-dimensional modes A and B being the generic example. However, it is not easy to physically realize the ideal flows owing to the presence of end effects and finite spanwise geometries. Flows past rings are sometimes advanced as providing a relevant idealization, but in fact these have symmetry group O(2) and only approach Z2 × O(2) symmetry in the infinite aspect ratio limit. The present work examines physically realizable periodically driven annular cavity flows that possess Z2 × O(2) spatio-temporal symmetry. The flows have three distinct codimension-1 instabilities: two synchronous modes (A and B), and two manifestations of a quasi-periodic (QP) mode, either as modulated standing waves or modulated travelling waves. It is found that the curvature of the system can determine which of these modes is the first to become unstable with increasing Reynolds number, and that even in the nonlinear regime near onset of three-dimensional instabilities the dynamics are dominated by mixed modes with complicated spatio-temporal structure. Supplementary movies illustrating the spatio-temporal dynamics are available at journals.cambridge. org/flm.
Effect of spatial learning on hippocampal testosterone in intact and castrated male rats.

BACKGROUND Sex steroids and their receptors exist in hippocampus and affect spatial learning and memory. This study was designed to measure testosterone level of CA1 and to assess the effect of spatial learning on its amount in left and right hippocampus of adult male rats. METHODS Sixteen rats were divided into two intact and castrated groups, and then trained in Morris water maze (MWM). Another 40 animals were divided into four groups and their right or left hippocampus cannulated. Half of the animals in each group were castrated simultaneously. All the animals were trained in MWM. Microdialysis was performed and steroid contents of hippocampal dialysate were analyzed through HPLC/ultraviolet detection device method. RESULTS Results showed no significant differences between control and castrated animals in spatial learning after four days of training. Gonadectomy did not change testosterone level in CA1 region of hippocampus. Spatial learning decreased testosterone levels in CA1 region of hippocampus in right hippocampus of the non-castrated group. Significant differences were indicated in testosterone level between left and right hippocampus, in favor of left side in all groups. CONCLUSION Castration does not affect learning. Testosterone, as a neuromodulator, exists in CA1 region of hippocampus and training can decrease its level only in right hippocampus significantly. Lesser testosterone content of right hippocampus may show the conversion of it to other metabolites.
Involvement in volunteering: an exploration of the personal experience of people with aphasia

This article reports results from a qualitative study in the UK of people with aphasia who have been involved in volunteering. The study describes their experiences; explores, from their perspective, the effects of involvement; and identifies key facilitators and barriers to the successful participation of people with aphasia in community activity. Data were collected by means of 10 individual semi-structured interviews using supported conversation techniques and through a focus group involving five more people. All participants had aphasia following a stroke. Average length of time since stroke for participants in the individual interviews was 5.6 years (range 3–12 years) and for participants in the focus group was 4.6 (range 1–10 years). Results are discussed according to four themes: (i) the effects of the activity on self; (ii) the effects on others; (iii) the effects on organisations hosting the activity and (iv) perceived barriers and facilitators impacting on volunteering. Implications are drawn for the promotion of participatory community activity within the matrix of therapeutic approaches and considered in light of previous studies that have reported the conceptualisations of people with aphasia about their lives and aspirations.