Notes

Heteroresistance to be able to beta-lactam antibiotics may possibly be described as a stage within the progression to be able to anti-biotic opposition.
The model uses a nurse-led, team-based approach that involves multiple professions working together to provide care for high-need, high-cost patients. Clinics use 4 simultaneous bundles of care that include evidence-based treatment guidelines, transitional care coordination activities, patient activation strategies, and behavioral health integration. Engaged patients indicate very high levels of satisfaction with care and improved physical and mental health outcomes resulting in significant cost savings for the health system. Finally, IPCP team members report joy in their work within the clinics.The generation of DNA double-strand breaks has historically been taught as the mechanism through which radiotherapy kills cancer cells. Recently, radiation-induced cytosolic DNA release and activation of the cGAS/STING pathway, with ensuing induction of interferon secretion and immune activation, have been recognized as important mechanisms for radiation-mediated anti-tumor efficacy. Here we demonstrate that radiation-induced activation of endogenous retroviruses (ERVs) also plays a major role in regulating the anti-tumor immune response during irradiation. Radiation-induced ERV-associated dsRNA transcription and subsequent activation of the innate antiviral MDA5/MAVS/TBK1 pathway led to downstream transcription of interferon-stimulated genes. Additionally, genetic knockout of KAP1, a chromatin modulator responsible for suppressing ERV transcription sites within the genome, enhanced the effect of radiation-induced anti-tumor response in vivo in two different tumor models. This anti-tumor response was immune-mediated and required an intact host immune system. Dimethindene mw Our findings indicate that radiation-induced ERV-dsRNA expression and subsequent immune response play critical roles in clinical radiotherapy, and manipulation of epigenetic regulators and the dsRNA-sensing innate immunity pathway could be promising targets to enhance the efficacy of radiotherapy and cancer immunotherapy.PURPOSE Some elderly patients (≥ 65 years old) with small-cell lung cancer (SCLC) do not receive chemotherapy likely because of fear of toxicity and uncertainty regarding benefits. Thus, we aimed to study real-world trends in utilization of antineoplastics over the years and predictors of utilization, survival, and Medicare expenditure in elderly patients with extensive-stage (ES) SCLC. PATIENTS AND METHODS Using the linked SEER and Medicare database, we identified elderly patients with newly diagnosed ES-SCLC between 2001 and 2013. The Wald test was used to determine the significance of trends. Cox proportional hazards models were applied for survival analyses. We used SAS, version 9.4 (SAS Institute, Cary, NC). RESULTS We identified 15,763 patients with newly diagnosed ES-SCLC. Approximately 6,838 patients (43.38%) received antineoplastics, and 8,925 patients (56.61%) received supportive care only. Every year since 2001, the percentage of patients receiving antineoplastics has decreased (45.8% v 36.6% in 20 of expensive novel agents.PURPOSE Unplanned emergency department (ED) visits and hospitalizations are common during systemic cancer therapy. To determine how patients with cancer trade off treatment benefit with risk of experiencing an ED visit or hospitalization when deciding about systemic therapy, we undertook a discrete choice experiment. MATERIALS AND METHODS Patients with breast, colorectal, or head and neck cancer contemplating, receiving, or having previously received systemic therapy were presented with 10 choice tasks (5 in the curative and 5 in the palliative setting) that varied on 3 attributes benefit, risk of ED visit, and risk of hospitalization. Preferences for attributes and levels were measured using part-worth utilities, estimated using hierarchical Bayes analysis. Segmentation analysis was conducted to identify subgroups with different preferences. RESULTS A total of 293 patients completed the survey; most were female (76%), had breast cancer (63%), and were currently receiving systemic therapy (72%) with curative intent (59%). Benefit was the most important decision attribute regardless of treatment intent, followed by risk of hospitalization, then risk of ED visit. Two segments were observed one large cluster exhibiting logical and consistent choices, and a smaller segment exhibiting illogical and inconsistent choices. Patients in the latter segment were more likely to have metastatic head and neck cancer, be male, were older, and reported fewer prior ED visits. CONCLUSION Although the risk of ED visit or hospitalization contributes to patient treatment preferences, benefit was the most important attribute. Segmentation suggests that a subset of patients may lack cognitive abilities, engagement, or literacy to consistently evaluate treatment choices. Understanding this subset may provide insight into patients' decision making and understanding of treatment options.BACKGROUND Urothelial carcinoma (UC) of the luminal molecular subtype is associated with lower rates of pathological upstaging from clinical stage T1-T2 to non-organ confined (NOC; ≥pT3 and/or pN+) disease at radical cystectomy (RC). However, approximately one-third of luminal UC were upstaged to NOC disease, and these patients may be undertreated if neoadjuvant chemotherapy (NAC) is withheld. Here, we trained a genomic classifier to predict luminal NOC disease in patients diagnosed with clinically organ confined (OC; cT1/T2) disease. MATERIALS & METHODS Specimens from transurethral resected high grade cT1-T2N0M0 UC of the bladder that belonged to the luminal subtype (Seiler 2017) were randomly split into training (n=75) and testing (n=25) sets for the development of a single-sample luminal upstaging classifier (LUC) using lasso/ridge-penalized logistic regression. All patients underwent RC without NAC and the primary endpoint was upstaging to NOC disease. A radical cystectomy and a platinum-treated NAC cohorof these patients.The Mitotic Exit Network (MEN), a budding yeast Ras-like signal transduction cascade, translates nuclear position into a signal to exit from mitosis. Here we describe how scaffolding the MEN onto spindle pole bodies (SPB - centrosome equivalent) allows the MEN to couple the final stages of mitosis to spindle position. Through the quantitative analysis of the localization of MEN components, we determined the relative importance of MEN signaling from the SPB that is delivered into the daughter cell (dSPB) during anaphase and the SPB that remains in the mother cell (mSPB). Movement of half of the nucleus into the bud during anaphase causes the active form of the MEN GTPase Tem1 to accumulate at the dSPB. In response to Tem1's activity at the dSPB the MEN kinase cascade, that functions downstream of Tem1, accumulates at both SPBs. This localization to both SPBs serves an important role in promoting efficient exit from mitosis. Cells that harbor only one SPB delay exit from mitosis. We propose that MEN signaling is initiated by Tem1 at the dSPB and that association of the downstream MEN kinases with both SPBs serves to amplify MEN signaling, enabling the timely exit from mitosis.
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