Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma:A Systematic Review

BACKGROUND: Understanding molecular pathogenesis of head and neck squamous cell carcinomas (HNSCC) has considerably improved in the last decades. As a result, novel therapeutic strategies have evolved, amongst which are epidermal growth factor receptor (EGFR)-targeted therapies. With the exception of cetuximab, targeted therapies for HNSCC have not yet been introduced into clinical practice. One important aspect of new treatment regimes in clinical practice is presence of robust biomarkers predictive for therapy response.METHODS: We performed a systematic search in PubMed, Embase and the Cochrane library. Articles were included if they investigated a biomarker for targeted therapy in the EGFR-PI3K-AKT-mTOR-pathway.RESULTS: Of 83 included articles, 52 were preclinical and 33 were clinical studies (two studies contained both a preclinical and a clinical part). We classified EGFR pathway inhibitor types and investigated the type of biomarker (biomarker on epigenetic, DNA, mRNA or protein level).CONCLUSION: Several EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers have been researched for HNSCC but few of the investigated biomarkers have been adequately confirmed in clinical trials. A more systematic approach is needed to discover proper biomarkers as stratifying patients is essential to prevent unnecessary costs and side effects.</p

Mental healthcare goes online:Practitioners' experiences of providing mental healthcare during the COVID-19 pandemic

The outbreak of the COVID-19 pandemic has necessitated sudden and radical changes in mental health care delivery, as strict social distancing and lockdown measures were imposed in the early phases of the pandemic. Almost overnight, practitioners were forced to transfer their face-to-face care practice to online means. To understand the implications of this drastic change for mental health care, and to improve the online care offerings, an online qualitative survey was held among mental health care professionals in Netherlands (n = 51). Our findings indicate that technological and usability problems pose a significant challenge, as do difficulties to establish rapport with clients. Moreover, not all mental health issues and treatment forms are equally amenable to online interaction. In contrast, in many instances, practitioners were positive about the effectiveness of treatment, and reported flexibility, a lower threshold for contact, and lack of travel time as advantages. Their most prominent needs concern better technological, organizational, and logistical support. It is critical that these needs are acted upon by institutions and governments. In addition, current results inform future research on the improvement of e-mental health technologies

Record RF performance of standard 90 nm CMOS technology

We have optimized 3 key RF devices realized in standard logic 90 nm CMOS technology and report a record performance in terms of n-MOS maximum oscillation frequency f/sub max/ (280 GHz), varactor tuning range and varactor and inductor quality factor

Interpretatie en discussie

The Unification of the Mediterranean World (400 BC - 400 AD

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, “hyper-pluripotent” state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency

Group composition impacts reproductive output and population viability in captive white rhinoceros

Captive breeding programmes can play an important role in the conservation of species threatened with extinction in the wild. White rhinoceros, Ceratotherium simum, have suffered drastic declines due to illegal poaching across their range, and captive populations have the potential to safeguard this species from extinction. However, white rhinoceros birth rates in captivity have been extremely low, and there is substantial variation in breeding success between different institutions. A better understanding of the factors limiting their reproduction in captivity could improve their breeding management and conservation potential. This study used studbook data (n = 467) and comparisons with wild populations in Kenya (n = 236) to assess the breeding performance and viability of the European captive southern white rhinoceros, Ceratotherium simum simum, population. Our results show that the European population is declining 2% annually under current demographic parameters. On average, just 10% of females calved annually, in comparison to almost 40% across wild populations. To become self-sustaining, this must increase to a minimum of 17%, though reaching this target may lead to additional management challenges. Further analyses using studbook (n = 134 individuals) and multi-institutional questionnaire data (n = 20 institutions) suggest that modifying the social structure of captive groups could improve female breeding success. Institutions housing larger groups had proportionally greater breeding success, and females were more likely to copulate if housed with another breeding female, and more receptive to bulls if housed in a group with a lower mean age. These findings highlight the importance of considering social conditions in captive breeding programmes, particularly for species with complex social systems and low reproductive rates

Understanding Palliative Cancer Chemotherapy: About Shared Decisions and Shared Trajectories

Most models of patient-physician communication take decision-making as a central concept. However, we found that often the treatment course of metastatic cancer patients is not easy to describe in straightforward terms used in decision-making models but is instead frequently more erratic. Our aim was to analyse these processes as trajectories. We used a longitudinal case study of 13 patients with metastatic colorectal and pancreatic cancer for whom palliative chemotherapy was a treatment option, and analysed 65 semi-structured interviews. We analysed three characteristics of the treatment course that contributed to the ‘erraticness’ of the course: (1) The treatment (with or without chemotherapy) contained many options; (2) these options were not stable entities to be decided upon, but changed identity over the course of treatment, and (3) contrary to the closure (option X means no option Y, Z, etc.) a decision implies, the treatment course was a continuous process in which options instead remained open. When the treatment course is characterised by these many and changeable options that do not result in closure, the shared decision-making model should take these into account. More attention needs to be paid to the erratic character of the process in which the doctor has to provide continuous information that is related to the changing situation of the patient; also, flexibility in dealing with protocols is warranted, as is vigilance about the overall direction of the process

Assessing professionals' adoption readiness for eMental health:Development and validation of the eMental health adoption readiness scale

BACKGROUND: The last few decades have witnessed significant advances in the development of digital tools and applications for mental health care. Despite growing evidence for their effectiveness, acceptance and use of these tools in clinical practice remain low. Hence, a validated and easy-to-use instrument for assessing professionals’ readiness to adopt eMental health (EMH) is necessary to gain further insights into the process of EMH adoption and facilitate future research on this topic. OBJECTIVE: The aim of this study is to develop and validate an instrument for assessing mental health care professionals’ readiness to adopt EMH. METHODS: Item generation was guided by literature and inputs from mental health care professionals and experts in survey development. Exploratory factor analyses were conducted on an initial set of 29 items completed by a sample of mental health care professionals (N=432); thereafter, the scale was reduced to 15 items in an iterative process. The factor structure thus obtained was subsequently tested using a confirmatory factor analysis with a second sample of mental health care professionals (N=363). The internal consistency, convergent validity, and predictive validity of the eMental Health Adoption Readiness (eMHAR) Scale were assessed. RESULTS: Exploratory factor analysis resulted in a 3-factor solution with 15 items. The factors were analyzed and labeled as perceived benefits and applicability of EMH, EMH proactive innovation, and EMH self-efficacy. These factors were confirmed through a confirmatory factor analysis. The total scale and subscales showed a good internal consistency (Cronbach α=.73-.88) along with acceptable convergent and predictive relationships with related constructs. CONCLUSIONS: The constructed eMHAR Scale showed a conceptually interpretable 3-factor structure having satisfactory characteristics and relationships with relevant concepts. Its ease of use allows for quick acquisition of data that can contribute to understanding and facilitating the process of adoption of EMH by clinical professionals

Prolonged (post-thaw) shelf life of −80°C frozen AB apheresis plasma

BACKGROUND: Early plasma transfusion is important in the treatment of patients with major hemorrhage. Prolonged shelf life of AB type frozen −80°C and cold-stored (4°C) deep frozen plasma (DFP) will improve strategic stock management, minimize need for resupply, and make pre-hospital implementation more feasible. METHODS AND MATERIALS: Plasma products type AB of different age and origin (−30°C Fresh Frozen [(FFP], −80°C DFP [short (±1 year) and long (±7 year)] stored) were thawed (Day 0), stored at 4°C, and sampled on Days 7 and 14. Additionally, samples of plasma containing blood products (Octaplas LG®, whole blood and platelets) were compared for coagulation factor activity, phospholipid clotting time (PPL), and kaolin TEG during 4°C or 22°C storage. RESULTS: Coagulation profiles of FFP, short- and long-stored −80°C DFP were not significantly different after thaw. Cold storage did not affect fibrinogen, Protein C, and Antithrombin III activities whereas factor V, VII, VIII, and Protein S decreased in all blood products. After 14 days DFP still meets the guidelines for clinical use, except for Protein S (0.4 IU/mL). With exception of Octaplas LG®, phospholipid activity and TEG coagulation were similar between plasma containing blood components during storage. CONCLUSION: AB DFP quality was unaffected by almost 7 years of frozen storage. Quality of thawed 14-day stored AB DFP met, with exception of Protein S, all minimal guidelines which implies that its quality is sufficient for use in the (pre)-hospital (military) environment for treatment of major hemorrhage