YAP-TEAD inhibition is associated with upregulation of an androgen receptor mediated transcription program providing therapeutic escape.

Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer-related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins.

Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry.

The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states.

Metabolome-wide association identifies altered metabolites and metabolic pathways in the serum of patients with cholangiocarcinoma.

Background & Aims: Metabolomic and lipidomic analyses provide an opportunity for novel biological insights. Cholangiocarcinoma (CCA) remains a highly lethal cancer with limited response to systemic, targeted, and immunotherapeutic approaches. Using a global metabolomics and lipidomics platform, this study aimed to discover and characterize metabolomic variations and associated pathway derangements in patients with CCA.

Baseline Characteristics and Use of Pretherapeutic 18 F-Fluorodeoxyglucose-PET for Pancreatic Cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy. Surgical resection is the only curative modality combined with neoadjuvant chemotherapy to improve survival. Given the limitations of traditional responses such as cross-sectional imaging (CT/MRI) or tumor markers, carbohydrate antigen 19-9 (CA19-9), the 2023 National Comprehensive Cancer Network guidelines included 18 F-fluorodeoxyglucose (FDG)-PET as an adjunct to assess response to neoadjuvant chemotherapy.

Noncanonical TRAIL Signaling Promotes Myeloid-Derived Suppressor Cell Abundance and Tumor Growth in Cholangiocarcinoma.

Background & Aims: Proapoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling as a cause of cancer cell death is a well-established mechanism. However, TRAIL-receptor (TRAIL-R) agonists have had very limited anticancer activity in human beings, challenging the concept of TRAIL as a potent anticancer agent. Herein, we aimed to define mechanisms by which TRAIL cancer cells can leverage noncanonical TRAIL signaling in myeloid-derived suppressor cells (MDSCs) promoting their abundance in murine cholangiocarcinoma (CCA).

Noncanonical TRAIL Signaling Promotes Myeloid-Derived Suppressor Cell Abundance and Tumor Progression in Cholangiocarcinoma.

Proapoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling as a cause of cancer cell death is a well-established mechanism. However, TRAIL-receptor (TRAIL-R) agonists have had very limited anticancer activity in humans, challenging the concept of TRAIL as a potent anticancer agent. Herein, we demonstrate that TRAIL cancer cells can leverage noncanonical TRAIL signaling in myeloid-derived suppressor cells (MDSCs) promoting their abundance in murine cholangiocarcinoma (CCA).

Immunobiology of cholangiocarcinoma.

Recent literature has significantly advanced our knowledge and understanding of the tumour immune microenvironment of cholangiocarcinoma. Detailed characterisation of the immune landscape has defined new patient subtypes. While not utilised in clinical practice yet, these novel classifications will help inform decisions regarding immunotherapeutic approaches.

Social participation and marital satisfaction in mid to late life marriage.

Objectives: Research shows that social participation is beneficial for overall health and well-being. Yet, no research to our knowledge has examined whether social participation is associated with greater marital satisfaction in middle-aged and older couples. We hypothesized that middle-aged and older adults would have greater marital satisfaction when their spouse engaged in social groups because there would be greater opportunity for self-expansion and for social support from ties outside the marriage.

Physiological correlates of support for self-expansion and links to goal pursuit in retirement.

Partner support for self-expansion has been associated with long-term health and retirement satisfaction, yet the underlying physiological correlates are unknown. We predicted that partner support for self-expansion would be associated with short-term physiology and behavior as well as long-term goal pursuit. And 100 couples with at least one retiree within 2 years of retirement visited the laboratory and had a discussion of the retirees' future goals for retirement.

Outcomes of pancreatectomy with portomesenteric venous resection and reconstruction for locally advanced pancreatic neuroendocrine neoplasms.

Background: While pancreatectomy with portomesenteric venous resection and reconstruction is commonly performed for locally advanced pancreatic adenocarcinoma, little is known regarding outcomes for pancreatic neuroendocrine neoplasms (panNENs).

Methods: Patients who underwent non-parenchyma-sparing pancreatectomy for panNENs at Mayo Clinic from 2000 to 2020 were retrospectively reviewed. Propensity score matching was performed and patient characteristics and outcomes compared.

Laughter and short-term blood pressure reactivity in middle-aged and older adult spousal support interactions.

Objective: Theories suggest that laughter decreases negative affect and enhances social bonds; however, no studies have examined the benefits of laughter on stress biomarkers in dyads. This study examined the hypotheses that individual and shared laughter would be associated with lower blood pressure reactivity and decreased self-reported and perceived partner distress for the target and spouse in a social support interaction.

Method: One hundred seventy-three middle-aged and older adult couples from a larger study were video-recorded, and their blood pressure was monitored continuously in the laboratory during a resting baseline, during a social support interaction in which they discussed a target's fear related to aging, and while playing a game (used as a comparison).

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and syndromic treatment of men with urethral discharge in Kingston, Jamaica, 2018-19.

Objectives: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered.

Methods: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N.

Fusidic acid resistance through changes in the dynamics of the drug target.

Antibiotic resistance in clinically important bacteria can be mediated by target protection mechanisms, whereby a protein binds to the drug target and protects it from the inhibitory effects of the antibiotic. The most prevalent source of clinical resistance to the antibiotic fusidic acid (FA) is expression of the FusB family of proteins that bind to the drug target (Elongation factor G [EF-G]) and promote dissociation of EF-G from FA-stalled ribosome complexes. FusB binding causes changes in both the structure and conformational flexibility of EF-G, but which of these changes drives FA resistance was not understood.

Growing into retirement: Longitudinal evidence for the importance of partner support for self-expansion.

Retirement can be a turbulent time of life in which people must navigate changes in their identity from ending a career and beginning a new phase of life. However, retirement can also provide opportunities for growth or self-expansion. We examined the benefits of partner support for self-expansion by using longitudinal evidence (at 3 time points) in a sample of 73 couples.

Congenital Cytomegalovirus and Hearing Loss: A Pilot Cross-Sectional Survey of Otologists' and Pediatric Otolaryngologists' Knowledge.

Objective: To evaluate pediatric otolaryngologists, neurotologists, and otologists on awareness and knowledge of congenital cytomegalovirus (cCMV).

Study Design: Pilot cross-sectional online survey.

Setting: Otolaryngology practices.

Dispersal of harmful fruit fly pests by international trade and a loop-mediated isothermal amplification assay to prevent their introduction.

Global trade of plant products represents one of the major driving forces for the spread of invasive insect pests. This visualization illustrates the problem of unintended dispersal of economically harmful fruit fly pests using geospatial maps based on interception data from the Swiss import control process. Furthermore, it reports the development of a molecular diagnostic assay for rapid identification of these pests at points of entry such as sea- and airports as a prevention measure.

A Loop-mediated Isothermal Amplification (LAMP) Assay for Rapid Identification of Bemisia tabaci.

The whitefly Bemisia tabaci (Gennadius) is an invasive pest of considerable importance, affecting the production of vegetable and ornamental crops in many countries around the world. Severe yield losses are caused by direct feeding, and even more importantly, also by the transmission of more than 100 harmful plant pathogenic viruses. As for other invasive pests, increased international trade facilitates the dispersal of B.

Privileges and penalties in the legal profession: an intersectional analysis of career progression.

Intersectionality theory is concerned with integrating social characteristics to better understanding complex human relations and inequalities in organizations and societies (McCall 2005). Recently, intersectionality research has taken a categorical and quantitative turn as scholars critically adopt but retain existing social categories to explain differences in labour market outcomes. A key contention is that social categories carry penalties or privileges and their intersection promotes or hinders the life chances of particular groups and individuals.

From laboratory to point of entry: development and implementation of a loop-mediated isothermal amplification (LAMP)-based genetic identification system to prevent introduction of quarantine insect species.

Background: Rapid genetic on-site identification methods at points of entry, such as seaports and airports, have the potential to become important tools to prevent the introduction and spread of economically harmful pest species that are unintentionally transported by the global trade of plant commodities. This paper reports the development and evaluation of a loop-mediated isothermal amplification (LAMP)-based identification system to prevent introduction of the three most frequently encountered regulated quarantine insect species groups at Swiss borders, Bemisia tabaci, Thrips palmi and several regulated fruit flies of the genera Bactrocera and Zeugodacus.

Results: The LAMP primers were designed to target a fragment of the mitochondrial cytochrome c oxidase subunit I gene and were generated based on publicly available DNA sequences.

Predicting the Pursuit and Support of Challenging Life Opportunities.

Deciding to embrace challenging opportunities may present one life context through which individuals may thrive, and these decisions may be influenced by one's significant relationships. Married couples were unobtrusively videotaped as one couple-member was presented with a challenging opportunity and decided whether to accept it. We assessed interpersonal predictors of the decision to accept or forgo the opportunity, predictors of the spouse's support during decision-making, and follow-up thriving outcomes 6 months later.