Discordant Situations Research Articles

Nomograms to predict the long-term prognosis for non-metastatic invasive lobular breast carcinoma: a population-based study

Invasive lobular breast carcinoma (ILC) is one potential subset that “clinicopathologic features” can conflict with “long-term outcome” and the optimal management strategy is unknown in such discordant situations. The present study aims to predict the long-term, overall survival (OS) and cancer-specific survival (CSS) of ILC. The clinical information of patients with non-metastatic ILC was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020. A total of 31451 patients were enrolled and divided into the training cohort (n=22,017) and validation cohort (n=9434). The last follow-up was December, 31, 2020 and the median follow-up period was 99 months (1–203). Age, marriage, estrogen (ER) status, progesterone (PR) status, grade, tumor size, lymph node ratio (LNR) and combined summary (CS) stage were prognostic factors for both OS and CSS of ILC, whereas chemotherapy and radiation were independent protect factors for OS. The nomograms exhibited satisfactory discriminative ability. For the training and validation cohorts, the C-index of the OS nomogram was 0.765 (95% CI 0.762–0.768) and 0.757 (95% CI 0.747–0.767), and the C-index of the CSS nomogram were 0.812 (95% CI 0.804–0.820) and 0.813 (95% CI 0.799–0.827), respectively. Additionally, decision curve analysis (DCA) demonstrated that the nomograms had superior predictive performance than traditional American Joint Committee on Cancer (AJCC) TNM stage. The novel nomograms to predict long-term prognosis based on LNR are reliable tools to predict survival, which may assist clinicians in identifying high-risk patients and devising individual treatments for patients with ILC. Our findings should aid public health prevention strategies to reduce cancer burden. We provide two R/Shiny apps (https://ilc-survival2024.shinyapps.io/osnomogram/; https://ilc-survival2024.shinyapps.io/cssnomogram/) to visualize findings.

Acercamientos y distanciamientos entre Costa Rica y la Revolución Cubana: algunas relaciones de hostilidad y deferencia

The article discusses how political ties between some governments in Costa Rica and Cuba have been since the triumph of the Cuban Revolution on January 1, 1959. Tensions, estrangement, and approximations between the two countries are shown. These relationships were conditioned by exacerbated anti-communism in the context of the Cold War and remained several years later. It is noted that, in all this time, the influence and interests of the United States were present in the relationships of these nations. Political (and personal) approaches that are not always recorded when talking about the links between these countries are taken into account. For this purpose, each government’s official statements and assertions regarding diplomatic ruptures and restorations in five decades are critically analyzed; it is also investigated in testimonial sources, videos and newspaper articles of some of the protagonists. They are two nations with different political regimes that, despite discordant situations, approaches, and collaborations prevailed over the sowing and cultivation of anti-communism

Language is brain: Improving neurologic health equity for linguistically diverse populations

Neurologic clinical care requires that clinicians gather and synthesize complex information, including a thorough, precise history and a detailed physical examination that maximizes the patient’s cooperation. Yet, for patients who do not speak the dominant language in the country or region where they live, effective communication with their clinician may not always occur. In this article, we discuss the impact of language on neurologic care, focusing on access to care and on the diagnosis and treatment of two common and potentially life-threatening conditions: stroke and epilepsy. We then review implications for clinical neurologic care as well as medical education and present evidence-based recommendations for improving neurologic health equity for linguistically diverse populations. Strategies should integrate professional medical interpreters (for oral communication) and translators (for written materials) into the neurologic team, account for families and caregivers in a culturally humble manner, and teach learners to apply clinical neurologic skills in both language-concordant and discordant situations.

Practical guidelines to manage discordant situations of SMN2 copy number in patients with spinal muscular atrophy.

ObjectiveAssessment of SMN2 copy number in patients with spinal muscular atrophy (SMA) is essential to establish careful genotype-phenotype correlations and predict disease evolution. This issue is becoming crucial in the present scenario of therapeutic advances with the perspective of SMA neonatal screening and early diagnosis to initiate treatment, as this value is critical to stratify patients for clinical trials and to define those eligible to receive medication. Several technical pitfalls and interindividual variations may account for reported discrepancies in the estimation of SMN2 copy number and establishment of phenotype-genotype correlations.MethodsWe propose a management guide based on a sequence of specified actions once SMN2 copy number is determined for a given patient. Regardless of the method used to estimate the number of SMN2 copies, our approach focuses on the manifestations of the patient to recommend how to proceed in each case.ResultsWe defined situations according to SMN2 copy number in a presymptomatic scenario of screening, in which we predict the possible evolution, and when a symptomatic patient is genetically confirmed. Unexpected discordant cases include patients having a single SMN2 copy but noncongenital disease forms, 2 SMN2 copies compatible with type II or III SMA, and 3 or 4 copies of the gene showing more severe disease than expected.ConclusionsOur proposed guideline would help to systematically identify discordant SMA cases that warrant further genetic investigation. The SMN2 gene, as the main modifier of SMA phenotype, deserves a more in-depth study to provide more accurate genotype-phenotype correlations.

Laparoscopic Simulation in Reverse and Side Alignment Impact on Forward Alignment Performance: A Randomized Controlled Trial.

The influence of visual-spatial discordance during training on laparoscopic skills is poorly understood. It has been proposed that training in visual-spatial discordant situations can improve performance in the forward alignment, which was the basis of our hypothesis. Our study's aim was to conduct a randomized control trial to explore the impact of simulated training in visual-spatial discordant situations on forward alignment performance. The participants were 80 medical students who were randomized into four groups. Group A served as the control and performed all peg transfers in the forward alignment. Groups B, C, and D experienced varied rounds of either increasing or decreasing sensorimotor discordance. The students were trained and tested using the peg transfer task used in the Fundamentals of Laparoscopic Surgery curriculum. Based on the group, each student performed 10 peg transfer practice rounds in their assigned alignment. After each practice session, each student was tested and scored in forward alignment performance. A baseline test, followed by three practice sessions, and three tests were done. Group A (control) demonstrated a statistically significant overall increase in scoring of 37.1% from baseline when compared to the final test. Groups B, C, and D showed improvements of 3.7%, 27.1%, and 19.3%, respectively, between baseline and the final test, yet none demonstrated consistent linear improvements. On multi-variate analysis, students who practiced in the side or reverse alignment positions scored 25 and 37 points lower, respectively, than students who practiced in the forward alignment. Our study suggests that training in visual-spatial discordant conditions does not lead to the development of forward alignment laparoscopic skills. This could have important implications when developing future laparoscopic skills training curriculums. To our knowledge, this is the largest study to date assessing the impacts of training in visual-spatial discordance situations on performance in the forward alignment.

B-cell lymphomas with discordance between pathological features and clinical behavior.

B-cell lymphomas encompass a large number of disease entities clinically ranging from indolent to aggressive. The defining pathological features usually predict clinical course, with small and large B-cell lymphomas correlating to low-grade vs high-grade features, but discordant situations may be encountered. Two sessions of the workshop of the XVIII meeting of the European Association for Haematopathology (EAHP) held in Basel in 2016 addressed this topic. One session illustrated various facets of "aggressiveness" in indolent lymphomas, either peculiar clinical manifestations, cytological variants, or unusual genetic features, as well as several examples of progression or transformation to a more aggressive disease. Another session exemplified large B-cell lymphomas with unexpected indolent behavior including cases arising in well-defined body compartments or in sanctuary sites. This paper describes the features of the cases presented in both groups, highlights the most salient points of discussion raised by the submitters and the panel, and summarizes current knowledge and recommendations relevant to diagnostic pathology practice.

Abstract 2486: Docetaxel resistant cells display cancer stem cell properties and regulate growth via PI3/Akt signaling

Abstract Both normal organogenesis and tumor development follow a Gompertzian growth curve. An understanding of the mechanisms operating in these apparently discordant situations, in which growth rate slows as mass increases, may be useful for the treatment of cancer. We have previously shown that encapsulating murine renal adenocarcinoma (RENCA) cells in a double layer of agarose to form spherical macrobeads, undergo Gompertzian growth regulation as tumor colonies within the confines of the inner agarose matrix. As the colonies reach maximal size, the RENCA macrobeads (MBs) secrete factors that also inhibit the proliferation of freely growing target cells outside the MB. In the current study, we report the ability of the tumor colonies within the MB to re-form following the debulking of tumor mass with docetaxel (0.5 μg/ml or 5.0 μg/ml). Docetaxel-resistant cells were assessed for the stem cell marker OCT4 using immunohistochemistry (Abcam ab19857), RT-PCR (Qiagen Cancer Stem Cell PCR Array) and cell migration/invasion (Corning Cell Migration Chemotaxis and Invasion Assay). Docetaxel-resistant cells are shown to be a discrete population of cells that exhibit stem cell-like properties, including prolonged quiescence (>16 wk), OCT4 staining, stem cell gene expression, increased migration and invasion, and in vivo tumor induction. These cancer stem-like properties are dose and time post-treatment dependent with the greatest expression observed in the few surviving cells at 6 wk post-treatment with 5 μg/ml. Tumor growth is observed in syngeneic BALB/c mice following transplantation of a single docetaxel-resistant cell at higher frequencies (≥ 6 of 9) as compared to the grafting of single monolayer cells (0 of 8) at 5 wk when using cells recovered at 6 wk from the 5 μg/ml dose treated MBs. To understand the mechanism of colony growth regulation within the MB, we hypothesized that tumor cells external to the MB would use similar growth control signaling when exposed to RENCA MBs or MB conditioned media. We have previously shown an increase in the activity of the transcription factor MEF2 in cells exposed to RENCA MB conditioned media. To investigate PI3/Akt signaling, a known pathway for MEF2 regulation, in human DU145 prostate tumor cells exposed to MB conditioned media, we used In-Cell and Western blotting. Exposure to RENCA MBs resulted in Akt hyperphosphorylation (≥ 48 hours) and de-phosphorylation of MEF2D in DU145 target cells. These findings support the hypothesis that RENCA MBs, as biological cell systems with the in vitro capability of inhibiting cancer cell proliferation, achieve this effect, at least in part, by signaling through Akt to regulate MEF2D. This effect is being investigated in colorectal patients with progressive disease, following informed consent, who underwent laparoscopic intraperitoneal implantations of RENCA MBs as part of ongoing clinical trials. Citation Format: Prithy C. Martis, Melissa A. Laramore, Hunter L. Gazda, Atira Dudley, Pradeep R. Dumpala, Allyson J. Ocean, Nathaniel Berman, Tapan Parikh, Zoe P. Andrada, Angelica Nazarian, Joanne Thomas, Eugene Akahoho, George Stoms, Alex Yaroshinsky, Thomas J. Fahey, David J. Wolf, Lawrence S. Gazda, Barry H. Smith. Docetaxel resistant cells display cancer stem cell properties and regulate growth via PI3/Akt signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2486.

Knowing between: generating boundary understanding through discordant situations in geographic–artistic research

The recent trend towards practice-based routes to knowledge has raised methodological questions concerning how best to research practices. Within the geography of art, the expansion over recent decades of collaborative and practice-based approaches has raised similar questions, along with concerns regarding the appropriateness of geographers not trained in art to undertake their own artistic practice within their research. This article grapples with these questions in relation to my own geographic–artistic research, through which I sought to generate boundary understanding or ‘knowing between’ different practices. I outline my own research method, which employed both qualitative interviews and practice-based research with artists, and present two case studies to highlight particular insights gained during the practice-based research, over and above those acquired through semi-structured interviews. These case studies reveal the insubstantial and fragile nature of boundaries between practices and levels of proficiency, and raise political issues for inter-disciplinary activities, problematizing in particular the role of the qualitative interview as a stand-alone method in research into practices, and recent calls for arts-based research only to be conducted by those proficient in art.

Place resists: grounding African urban order in an age of global change

Emerging studies of African urbanity are reappraising city‐making practices and theories in ‘the global South’. Grounding alternative claims to ‘cityness’, the dynamics of informality hold a key to local cultures of transformation. In our age of global change this insight is crucial to grasping future urban demands. What debate about such cities calls for is an interpretive model able to orient circumstantial judgments in often discordant situations. Emphasising the anchoring role of place, the research argues for a research analytic more faithful to everyday events than ‘Northern’ paradigms of urban order. Concepts of order underpin profound questions of orientation: how do African city dwellers make sense of their expectations? What role does the city play in decision‐making? Being true to how life is experienced on the ground implies comprehending its challenges, but interpretation must go beyond simply identifying with the disadvantaged. The plurality of claims to the city creates conflicts that typically obscure deeper issues. Understanding rooted in the mundane order would disclose a concrete metabolism able to mediate rivalry between urban discourses. Instead of a consensus version of what makes a city civic, the proposed analytic follows ideas in planning theory and social processes to address everyday diversity head on.

Comparative analysis of the effects of sample source and test methodology on the assessment of protein expression in acute myelogenous leukemia

Numerous studies have analyzed the expression and prognostic importance of various proteins in acute myelogenous leukemia (AML). We sought to determine whether the sample source and methodology used to measure protein expression affect the results obtained. To determine the importance of sample source, we used Western blotting to compare the expression of eight proteins and phosphoproteins in the leukemia blast-enriched fraction of 118 blood- and 108 marrow-derived samples, including 37 paired samples. To determine the importance of methodology, the expression of five proteins was measured in 20 paired samples by Western blotting, laser scanning cytometry (LSC), and flow cytometry. The mean expression and range of expression in blood- and marrow-derived samples were statistically identical for all eight proteins. Expression measurements for the 37 paired blood and marrow samples also had very high statistical correlation. The LSC and flow cytometry data had the highest concordance when compared using Kolmogorov-Smirnoff D-stats (range of R values, 0.8-1.0). High concordance was also observed between the LSC and flow cytometry results when the percentage of cells positive for expression was dichotomized into positive or negative expression. However, there was less correlation between LSC and flow cytometry when the actual percentages of positive cells were compared. The majority of discordant situations involved samples that were positive by flow cytometry but negative by LSC. The correlation between Western blotting signal intensity and the percentage of expression-positive cells measured by LSC or flow cytometry varied by protein but was limited when there was little heterogeneity in expression by either method. In conclusion, provided that leukemia blast-enriched fractions were analyzed, the blood- and marrow-derived samples had identical protein expression. There was good concordance of results between flow cytometry and LSC, which share similar technology, but more limited correlation between these methods and Western blotting.

In vitro xenorecognition of adult pig pancreatic islet cells by splenocytes from nonobese diabetic or non-diabetes-prone mice.

In vitro studies of the nonobese diabetic (NOD) mouse prone to type 1 autoimmune diabetes were conducted in order to investigate the mechanisms possibly involved in cell-mediated rejection of adult pig islet xenografts. Mouse cellular proliferation in discordant situations was previously investigated only with stimulator lymphocytes and found to be low in intensity and due to an indirect recognition mechanism involving murine antigen-presenting cells (APC). It was also important to characterize murine anti-pig islet response. In the present study, mouse splenocytes responded to pig islet cells since primary proliferations were detected in non-diabetes-prone Balb/c (P<0.04) or NOD (P<0.001) mice. Moreover, NOD mice displayed a higher (P<0.003) splenocyte response to pig islet cells (stimulation index: 5.8+/-0.7) than did Balb/c mice (stimulation index: 2.3+/-0.3), whereas responses to pig stimulator splenocytes were similar in both strains. The proliferation of NOD splenocytes to pig islet cells was lower (P<0.0001) than the allogeneic response to Balb/c islet cells but similar to syngeneic proliferation to NOD islet cells. In both NOD and Balb/c mice, splenocyte proliferation to pig islet cells was abolished (P<0.01) when CD4+ cells were blocked with antibodies, whereas the blocking of CD8+ cells had a nonsignificant effect. The main T-splenocyte subsets involved were restricted to mouse MHC class II molecules as they did not proliferate in the presence of monoclonal antibodies directed at I-A molecules. NOD and Balb/c splenocyte proliferation to pig islet cells was abolished after removal of plastic-adherent APC, which indicates that the major activation pathway was indirect. Purified CD4+ or CD8- cells alone did not proliferate in response to pig islet cells but recovered a proliferative ability when mixed with APC. CD4- cells, alone or in the presence of APC, were not capable of responding to pig islet cells. Both Th1 and Th2 splenocytes were involved in response to pig islet cells since interferon-gamma (IFN-gamma) and interleukin (IL-)-4 production increased significantly (300-fold and 11-fold, respectively, P<0.02 for both), whereas the increase in IL-10 production was much lower (only 1.5-fold). The IFN-gamma/IL-4 and IFN-gamma/IL-10 ratios stimulated by pig islet cells were not different with NOD and Balb/c splenocytes. In conclusion, mouse cell-mediated reaction against xenogeneic adult pig islet cells mainly involves class II-restricted CD4+ T lymphocytes of Th1 and Th2 subtypes, with an indirect pathway for the recognition. Although of low intensity, this cell-mediated reaction constitutes an obstacle to pig islet engraftment in the mouse, although one not necessarily more insurmountable than alloreactivity. The peculiarity of NOD mouse splenocytes, in terms of proliferation against pig islets, suggests that the study of islet xenograft rejection should take the immunogenetic context of diabetes into account, in which case the use of non-diabetes-prone mice has its limitations.

Lymphocyte subpopulations in immunodeficiency disorders: I. Human thymus-lymphoid tissue antigen

Peripheral blood lymphocytes from 25 normal persons and 47 patients with immunodeficiency diseases were studied for the presence of human thymus-lymphoid tissue antigen (HTLA) and their responsiveness to PHA. Whereas in normal persons, HTLA values were consistently around 36%, 17 immunodeficient patients had low numbers of HTLA-positive lymphocytes in their peripheral blood. In general, HTLA values corresponded with PHA responsiveness ( 36 47 ), however, a number of discordant situations were observed. These results suggest that HTLA may be a useful marker in evaluating an immunologically relevant lymphocyte population in clinical situations. This population is most likely of thymus origin (4,5) and appears to be associated with PHA responsiveness in most situations. On the other hand, the dissociation of these markers in 11 patients suggests that they detect either distinct but overlapping populations, different phases of differentiation of a single lymphocyte population or that the cells involved may be perturbed independently by exogenous factors, such as infections.