Notes

Palbociclib inside cancer of the breast neoadjuvant environment.
Purpose Sorafenib leads to clinical benefit in a subgroup of patients, while all are exposed to potential toxicity. Currently, no predictive biomarkers are available. The purpose of this study was to evaluate whether 11C-sorafenib and 15O-H2O PET have potential to predict treatment efficacy. Methods In this prospective exploratory study, 8 patients with advanced solid malignancies and an indication for sorafenib treatment were included. Microdose 11C-sorafenib and perfusion 15O-H2O dynamic PET scans were performed before and after two weeks of sorafenib therapy. The main objective was to assess whether tumor 11C-sorafenib uptake predicts sorafenib concentrations during therapy in corresponding tumor biopsies measured with liquid chromatography tandem mass spectrometry (LC-MS/MS). Secondary objectives included the association of 11C-sorafenib PET, perfusion 15O-H2O PET and sorafenib concentrations after therapeutic dosing with response. Results11C-sorafenib PET did not predict sorafenib concentrations in tumor biopsies during therapy. In addition, sorafenib plasma and tumor concentrations, were not associated with clinical outcome in this exploratory study. Higher 11C-sorafenib accumulation in tumors at baseline and day 14 of treatment showed association with poorer prognosis and was correlated with tumor perfusion (rs = 0.671, P = 0.020). Interestingly, a decrease in tumor perfusion measured with 15O-H2O PET after only 14 days of therapy showed an association with response, with a decrease in tumor perfusion of 56% ± 23% (mean ± SD) versus 18% ± 32% in patients with stable and progressive disease, respectively. Conclusion Microdose 11C-sorafenib PET did not predict intratumoral sorafenib concentrations after therapeutic dosing, but the association between a decrease in tumor perfusion and clinical benefit warrants further investigation.Fibroblast activation protein (FAP), a membrane-anchored peptidase, is highly expressed in cancer-associated fibroblasts in more than 90% of epithelial tumors and contributes to progression and worse prognosis of different cancers. FSEN1 purchase Therefore, FAP is considered a promising target for radionuclide-based approaches for diagnosis and treatment of tumors and for the diagnosis of nonmalignant diseases associated with a remodeling of the extracellular matrix. Accordingly, a variety of quinolone-based FAP inhibitors (FAPIs) coupled to chelators were developed displaying specific binding to human and murine FAP with a rapid and almost complete internalization. Because of a high tumor uptake and a very low accumulation in normal tissues, as well as a rapid clearance from the circulation, a high contrast is obtained for FAPI PET/CT imaging even at 10 min after tracer administration. Moreover, FAPI PET/CT provides advantages over 18F-FDG PET/CT in several tumor entities for initial staging and detection of tumor recurrence and metastases, including peritonitis carcinomatosa.
There has been a lack of studies on the types and severity of drug-related problems (DRPs) in hospitalised patients with Parkinson's disease (PD) in China until now.

To investigate the types and causes of DRPs, and to assess the severity of these DRPs in PD patients in neurology wards.

A retrospective study involving 209 PD inpatients was conducted at a tertiary hospital in China from January 2017 to December 2018. The identification and assessment of DRPs were based on the Pharmaceutical Care Network Europe (PCNE) tool version 8.03. The severity ratings of these DRPs was assessed based on the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) classification.

A total of 274 DRPs with an average of 1.31±1.00 problems per patient were identified, in which 83.3% of the population had at least one DRP. Using the PCNE classification system, the most common domain of DRPs was "Other, P3" (62.8%), followed by "Treatment effectiveness, P1" (19.3%) and "Treatment safety, P2" (17.9%). A total of 88.7% of the DRPs were rated at severity categories B to D (causing no or potential harm), whereas 11.3% were rated as categories E to H (causing actual harm).

These data indicate that the prevalence of DRPs is high among PD patients. The identification of different subtypes of DRPs may facilitate risk reduction for PD patients.
These data indicate that the prevalence of DRPs is high among PD patients. The identification of different subtypes of DRPs may facilitate risk reduction for PD patients.This study addresses the existing gap in literature that ethnographically examines the experiences of Spanish-speaking patients with limited English proficiency in clinical spaces. All of the participants in this study presented to the emergency department (ED) for evaluation of non-urgent health conditions. Patient shadowing was employed to explore the challenges that this population face in unique clinical settings like the ED. This relatively new methodology facilitates obtaining nuanced understandings of clinical contexts under study in ways that quantitative approaches and survey research do not. Drawing from the field of medical anthropology and approach of narrative medicine, the collected data are presented through the use of clinical ethnographic vignettes and thick description. The conceptual framework of health-related deservingness guided the analysis undertaken in this study. Structural stigma was used as a complementary framework in analysing the emergent themes in the data collected. The results and analysis from this study were used to develop an argument for the consideration of language as a distinct social determinant of health.This article is concerned with the visual culture of global health data using antimicrobial resistance (AMR) as an example. I explore how public health data and knowledge are repackaged into visualisations and presented in four contemporary genres the animation, the TED Talk, the documentary and the satire programme. I focus on how different actors describe a world in which there are no or few antibiotics that are effective against bacterial infections. link2 I examine the form, content and style of the visual cultural of AMR, examining how these genres tell a story of impending apocalypse while also trying to advert it. This is a form of story-telling based around the if/then structure we are told that if we do not take certain actions today, then we will face a postantibiotic future with certain, often catastrophic, consequences. Within this if/then structure, there are various aims and objectives the goal may be preventing further spread of AMR, building awareness or pushing for certain policy or funding decisions. These stories also serve to place or deflect blame, on animals, occupations, patients, industries and others and to highlight risks and consequences. These examples share similarities in the forms of story-telling and narrative, and in the use of specific data sources and other images. By using several Swedish examples, I demonstrate how global data are reinterpreted for a national audience. Overall, I argue that while the convergence of a dominant narrative indicates scientific consensus, this consensus also stifles our collective imagination in finding new solutions to the problem. Finally, I also use the example of AMR to discuss the need for a broader social science and humanities engagement with the visual culture of global health data.
Breaking bad news about life-threatening and possibly terminal conditions is a crucial part of paediatric care for children in this situation. Little is known about how the parents of children with life-threatening conditions experience communication of bad news. The objective of this study is to analyse parents' experiences (barriers and facilitators) of communication of bad news.

A qualitative study consisting of a constant comparative analysis of in-depth interviews conducted with parents.

The Netherlands.

Sixty-four parents-bereaved and non-bereaved-of 44 children (aged 1-12 years, 61% deceased) with a life-threatening condition.

None.

Based on parents' experiences, the following 10 barriers to the communication of bad news were identified (1) a lack of (timely) communication, (2) physicians' failure to ask parents for input, (3) parents feel unprepared during and after the conversation, (4) a lack of clarity about future treatment, (5) physicians' failure to voice uncertainties, (6) physiciano better suit the needs of parents. From the parents' perspective, the timing of conversations in which they were informed that their child might not survive was far too late. Sometimes, no such conversations ever took place.Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.The presence of polyfunctional CD4+ T cells is often associated with favorable antitumor immunity. We report here that persistent activation of signal transducer and activator of transcription 5 (STAT5) in tumor-specific CD4+ T cells drives the development of polyfunctional T cells. link3 We showed that ectopic expression of a constitutively active form of murine STAT5A (CASTAT5) enabled tumor-specific CD4+ T cells to undergo robust expansion, infiltrate tumors vigorously, and elicit antitumor CD8+ T cell responses in a CD4+ T cell adoptive transfer model system. Integrated epigenomic and transcriptomic analysis revealed that CASTAT5 induced genome-wide chromatin remodeling in CD4+ T cells and established a distinct epigenetic and transcriptional landscape. Single-cell RNA sequencing analysis further identified a subset of CASTAT5-transduced CD4+ T cells with a molecular signature indicative of progenitor polyfunctional T cells. The therapeutic significance of CASTAT5 came from our finding that adoptive transfer of T cells engineered to coexpress CD19-targeting chimeric antigen receptor (CAR) and CASTAT5 gave rise to polyfunctional CD4+ CAR T cells in a mouse B cell lymphoma model. The optimal therapeutic outcome was obtained when both CD4+ and CD8+ CAR T cells were transduced with CASTAT5, indicating that CASTAT5 facilitates productive CD4 help to CD8+ T cells. Furthermore, we provide evidence that CASTAT5 is functional in primary human CD4+ T cells, underscoring its potential clinical relevance. Our results implicate STAT5 as a valid candidate for T cell engineering to generate polyfunctional, exhaustion-resistant, and tumor-tropic antitumor CD4+ T cells to potentiate adoptive T cell therapy for cancer.
As the manual creation and maintenance of biomedical ontologies are labor-intensive, automatic aids are desirable in the lifecycle of ontology development.

Provided with a set of concept names in the Foundational Model of Anatomy (FMA), we propose an innovative method for automatically generating the taxonomy and the partonomy structures among them, respectively.

Our approach comprises 2 main tasks The first task is predicting the direct relation between 2 given concept names by utilizing word embedding methods and training 2 machine learning models, Convolutional Neural Networks (CNN) and Bidirectional Long Short-term Memory Networks (Bi-LSTM). The second task is the introduction of an original granularity-based method to identify the semantic structures among a group of given concept names by leveraging these trained models.

Results show that both CNN and Bi-LSTM perform well on the first task, with F1 measures above 0.91. For the second task, our approach achieves an average F1 measure of 0.79 on 100 case studies in the FMA using Bi-LSTM, which outperforms the primitive pairwise-based method.
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