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Evolutionary theorists propose that people's mate value influences the types of mates they select and their estimates of whether potential mates would select them. Social anxiety has the potential to be a characteristic that is associated with low perceived mate value and, therefore, to influence the mate selection process. In the present study, socially anxious (n = 63) and nonanxious (n = 62) participants were presented with a series of photographs and accompanying narrative descriptions of opposite sex individuals representing varying levels of physical attractiveness and social status. They were instructed to rate (a) the likelihood in which they would engage in various relationship and sexual behaviors with similar people, and (b) the likelihood in which similar people would want to engage in these relationship and sexual behaviors with them. Relative to nonanxious participants, socially anxious participants estimated that they would be less likely to initiate these behaviors with physically attractive people and more likely to initiate these behaviors with physically unattractive people. Moreover, they consistently estimated that others would be less likely to engage in these behaviors with them. These results raise the possibility that socially anxious individuals' low perception of their own mate value influences the partners with whom they enter into relationships. [PUBLICATION ABSTRACT]

The tickets were a snip for pounds 20 and, yes, she was clearly not at her best, but how the behaviours of those people who booed her have contributed to her already fragile state of mind...

Background The clonoSEQ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) identifies and tracks unique disease-associated immunoglobulin (Ig) sequences by next-generation sequencing of IgH, IgK, and IgL rearrangements and IgH-BCL1/2 translocations in malignant B cells. Here, we describe studies to validate the analytical performance of the assay using patient samples and cell lines. Methods Sensitivity and specificity were established by defining the limit of detection (LoD), limit of quantitation (LoQ) and limit of blank (LoB) in genomic DNA (gDNA) from 66 patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), or chronic lymphocytic leukemia (CLL), and three cell lines. Healthy donor gDNA was used as a diluent to contrive samples with specific DNA masses and malignant-cell frequencies. Precision was validated using a range of samples contrived from patient gDNA, healthy donor gDNA, and 9 cell lines to generate measurable residual disease (MRD) frequencies spanning clinically relevant thresholds. Linearity was determined using samples contrived from cell line gDNA spiked into healthy gDNA to generate 11 MRD frequencies for each DNA input, then confirmed using clinical samples. Quantitation accuracy was assessed by (1) comparing clonoSEQ and multiparametric flow cytometry (mpFC) measurements of ALL and MM cell lines diluted in healthy mononuclear cells, and (2) analyzing precision study data for bias between clonoSEQ MRD results in diluted gDNA and those expected from mpFC based on original, undiluted samples. Repeatability of nucleotide base calls was assessed via the assay’s ability to recover malignant clonotype sequences across several replicates, process features, and MRD levels. Results LoD and LoQ were estimated at 1.903 cells and 2.390 malignant cells, respectively. LoB was zero in healthy donor gDNA. Precision ranged from 18% CV (coefficient of variation) at higher DNA inputs to 68% CV near the LoD. Variance component analysis showed MRD results were robust, with expected laboratory process variations contributing ≤3% CV. Linearity and accuracy were demonstrated for each disease across orders of magnitude of clonal frequencies. Nucleotide sequence error rates were extremely low. Conclusions These studies validate the analytical performance of the clonoSEQ Assay and demonstrate its potential as a highly sensitive diagnostic tool for selected lymphoid malignancies.

Inhibition of the vascular endothelial growth factor (VEGF) pathway has failed to improve overall survival of patients with glioblastoma (GBM). We previously showed that angiopoietin-2 (Ang-2) overexpression compromised the benefit from anti-VEGF therapy in a preclinical GBM model. Here we investigated whether dual Ang-2/VEGF inhibition could overcome resistance to anti-VEGF treatment. We treated mice bearing orthotopic syngeneic (Gl261) GBMs or human (MGG8) GBMxenografts with antibodies inhibiting VEGF (B20), or Ang-2/VEGF (CrossMab, A2V). We examined the effects of treatment on the tumor vasculature, immune cell populations, tumor growth, and survival in both the Gl261 and MGG8 tumor models. We found that in the Gl261 model, which displays a highly abnormal tumor vasculature, A2V decreased vessel density, delayed tumor growth, and prolonged survival compared with B20. In the MGG8 model, which displays a low degree of vessel abnormality, A2V induced no significant changes in the tumor vasculature but still prolonged survival. In both the Gl261 and MGG8 models A2V reprogrammed protumor M2 macrophages toward the antitumor M1 phenotype. Our findings indicate that A2V may prolong survival in mice with GBM by reprogramming the tumor immune microenvironment and delaying tumor growth.

Antiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types. However, an incomplete understanding of the mechanisms of action of antiangiogenic agents has hindered optimization and broader application of this new therapeutic modality. In particular, the impact of antiangiogenic therapy on tumor blood flow and oxygenation status (i.e., the role of vessel pruning versus normalization) remains controversial. This controversy has become critical as multiple phase III trials of anti-VEGF agents combined with cytotoxics failed to show overall survival benefit in newly diagnosed glioblastoma (nGBM) patients and several other cancers. Here, we shed light on mechanisms of nGBM response to cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, using MRI techniques and blood biomarkers in prospective phase II clinical trials of cediranib with chemoradiation vs. chemoradiation alone in nGBM patients. We demonstrate that improved perfusion occurs only in a subset of patients in cediranib-containing regimens, and is associated with improved overall survival in these nGBM patients. Moreover, an increase in perfusion is associated with improved tumor oxygenation status as well as with pharmacodynamic biomarkers, such as changes in plasma placenta growth factor and sVEGFR2. Finally, treatment resistance was associated with elevated plasma IL-8 and sVEGFR1 posttherapy. In conclusion, tumor perfusion changes after antiangiogenic therapy may distinguish responders vs. nonresponders early in the course of this expensive and potentially toxic form of therapy, and these results may provide new insight into the selection of glioblastoma patients most likely to benefit from anti-VEGF treatments.

Nursing practice is diverse, with nurses serving in both direct and indirect patient care roles. For nurse educators, the realm of nursing practice extends beyond direct patient care to include preparing students for nursing practice. Academic nurse educators must be prepared to serve as educators, researchers, and to have experience in a clinical specialty area. For many nurse educators, advanced academic preparation often relates to a clinical area of practice rather than pedagogical practice. Graduate-level knowledge of evidence-based research and practice, teaching methods, and curriculum design and development form the foundation for academic practice. Because education and nursing are two distinctive disciplines, clinical expertise does not naturally result in teaching expertise. Lack of consensus regarding the educational preparation of nurse educators adds to the complexity of the nursing profession. The purpose of this article is to advocate for pedagogical preparation for academic nurse educators. Additionally, this article contains recommendations for pedagogical competencies indicative of academic nurse educator preparation.

Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole‐genome sequencing was performed along with single telomere length analysis (STELA). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.

Nurses and nursing students may need help understanding the connection between research and practice. Nursing students and clinical nurse leaders worked together to review institutional policies and make recommendations based on the strongest research evidence. In this column, the authors describe how they created a meaningful connection between research and clinical nursing practice for undergraduate nursing students and the benefits to the health system from this innovative program. [ J Contin Educ Nurs . 2023;54(10):441–443.]

Pathogenic germline variants in telomerase ( TERT ) cause telomere biology disorders (TBDs) and are associated with bone marrow failure, pulmonary fibrosis, and other complications. TERT c.3150 G > C (p.K1050N) is frequent in the Ashkenazi Jewish (ASH) population and has been identified in ASH families with TBDs. Whole-genome sequencing of 96 p.K1050N heterozygotes from the UK Biobank and All of Us databases revealed a shared haplotype block, supporting a founder effect. Analyses of 15 additional p.K1050N cases validated this haplotype and identified mitochondrial and Y-STR haplogroups consistent with ASH ancestry. Clinical assessments showed that p.K1050N contributes to TBD phenotypes and shortened telomeres, while population data suggest incomplete penetrance. p.K1050N reduces telomerase activity and processivity, and decreases PCNA expression and BrdU incorporation, impairing cell proliferation. Our findings establish TERT p.K1050N as an ASH founder variant associated with TBDs, underscoring the need for genetic screening and long-term clinical studies.

Committee Leadership In fall 2013, the faculty senate appointed the Academic Core Curriculum Committee (ACCC), thirteen faculty members from across the three colleges, to lead the reform process. [...]understanding how to design learningcentered courses is a critical component of their role. In anticipation of the potential impact of this campus-wide event and the possible alignment with the new curriculum goals, the directors of General Education and the CAFE developed a grant-funded teaching program encouraging faculty to develop integrative courses focused on presidential elections and/or political debate. TAKEAWAYS Our takeaways and advice to others who are planning general education reform efforts are featured in the bulleted list below. * Be open to a fluid and transparent process that involves a great deal of communication and listening. * Maintain a continued pragmatism with an attitude toward experimentation. * Adopt a stance of confident humility, in which you acknowledge you may not have all the answers or be able to anticipate all the questions, but that you will work together to discover them. * Recognize that large-scale curricular change is a process involving individual faculty, academic programs, and the larger institutional culture. * Convene a diverse committee representing stakeholders with varied experiences with general education, institutional history, and leadership responsibilities. * Understand academic culture, faculty readiness, and external and institutional administration expectations.