Efficiently exploring the causal role of contextual moderators in behavioral science.

Behavioral science interventions have the potential to address longstanding policy problems, but their effects are typically heterogeneous across contexts (e.g., teachers, schools, and geographic regions). This contextual heterogeneity is poorly understood, however, which reduces the field's impact and its understanding of mechanisms. Here, we present an efficient way to interrogate heterogeneity and address these gaps in knowledge. This method a) presents scenarios that vividly represent different moderating contexts, b) measures a short-term behavioral outcome (e.g., an academic choice) that is known to relate to typical intervention outcomes (e.g., academic achievement), and c) assesses the causal effect of the moderating context on the link between the psychological variable typically targeted by interventions and this short-term outcome. We illustrated the utility of this approach across four experiments (total n = 3,235) that directly tested contextual moderators of the links between growth mindset, which is the belief that ability can be developed, and students' academic choices. The present results showed that teachers' growth mindset-supportive messages and the structural opportunities they provide moderated the link between students' mindsets and their choices (studies 1 to 3). This pattern was replicated in a nationally representative sample of adolescents and did not vary across demographic subgroups (study 2), nor was this pattern the result of several possible confounds (studies 3 to 4). Discussion centers on how this method of interrogating contextual heterogeneity can be applied to other behavioral science interventions and broaden their impact in other policy domains.

Artificial Intelligence Assisted Surgical Scene Recognition: A Comparative Study Amongst Healthcare Professionals.

OBJECTIVE: This study aimed to compare the ability of a deep-learning platform (the MACSSwin-T model) with healthcare professionals in detecting cerebral aneurysms from operative videos. Secondly, we aimed to compare the neurosurgical team's ability to detect cerebral aneurysms with and without AI-assistance. BACKGROUND: Modern microscopic surgery enables the capture of operative video data on an unforeseen scale. Advances in computer vision, a branch of artificial intelligence (AI), have enabled automated analysis of operative video. These advances are likely to benefit clinicians, healthcare systems, and patients alike, yet such benefits are yet to be realised. METHODS: In a cross-sectional comparative study, neurosurgeons, anaesthetists, and operating room (OR) nurses, all at varying stages of training and experience, reviewed still frames of aneurysm clipping operations and labelled frames as "aneurysm not in frame" or "aneurysm in frame". Frames then underwent analysis by the AI platform. A second round of data collection was performed whereby the neurosurgical team had AI-assistance. Accuracy of aneurysm detection was calculated for human only, AI only, and AI-assisted human groups. RESULTS: 5,154 individual frame reviews were collated from 338 healthcare professionals. Healthcare professionals correctly labelled 70% of frames without AI assistance, compared to 78% with AI-assistance (OR 1.77, P<0.001). Neurosurgical Attendings showed the greatest improvement, from 77% to 92% correct predictions with AI-assistance (OR 4.24, P=0.003). CONCLUSION: AI-assisted human performance surpassed both human and AI alone. Notably, across healthcare professionals surveyed, frame accuracy improved across all subspecialties and experience levels, particularly among the most experienced healthcare professionals. These results challenge the prevailing notion that AI primarily benefits junior clinicians, highlighting its crucial role throughout the surgical hierarchy as an essential component of modern surgical practice.

The "Difficult" Inpatient, a Qualitative Study of Physician Perspectives.

BACKGROUND: Previous studies exploring difficult inpatients have mostly focused on psychiatric inpatients. OBJECTIVE: To explore the characteristics of difficult medicine inpatients. DESIGN: Qualitative study using focus groups and semi-structured interviews. Transcripts were recorded, transcribed, and coded (MAXQDA) using thematic content analysis. PARTICIPANTS: Medicine inpatient providers at a tertiary care facility. KEY RESULTS: Our sample consisted of 28 providers (6 hospitalists, 10 medicine attendings, 6 medicine residents, and 6 interns). Theme 1: Provider experience: Difficult inpatients were time-consuming and evoked emotional responses including frustration and dysphoria. Theme 2: Patient characteristics: Included having personality disorders or mental health issues, being uncooperative, manipulative, angry, demanding, threatening, or distrustful. Difficult patients also had challenging social situations and inadequate support, unrealistic care expectations, were self-destructive, tended to split care-team messages, and had unclear diagnoses. Theme 3: Difficult families: Shared many characteristics of difficult patients including being distrustful, demanding, manipulative, threatening, or angry. Difficult families were barriers to care, disagreed with the treatment plan and each other, did not act in the patient's best interest, suggested inappropriate treatment, or had unrealistic expectations. STRATEGIES: Approaches to dealing with difficult patients or families included building trust, being calm, and having a consistent message. Communication approaches included naming the emotion, empathetic listening, identifying patient priorities and barriers, and partnering. CONCLUSIONS: Difficult patients induced emotional responses, dysphoria, and self-doubt among providers. Underlying personality disorders were often mentioned. Difficult patients and families shared many characteristics. Communication and training were highlighted as key strategies.

Comprehensive safety assessment of serendipity berry sweet protein produced from Komagataella phaffii.

Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day.

Open science, communal culture, and women's participation in the movement to improve science.

Science is undergoing rapid change with the movement to improve science focused largely on reproducibility/replicability and open science practices. This moment of change-in which science turns inward to examine its methods and practices-provides an opportunity to address its historic lack of diversity and noninclusive culture. Through network modeling and semantic analysis, we provide an initial exploration of the structure, cultural frames, and women's participation in the open science and reproducibility literatures (n = 2,926 articles and conference proceedings). Network analyses suggest that the open science and reproducibility literatures are emerging relatively independently of each other, sharing few common papers or authors. We next examine whether the literatures differentially incorporate collaborative, prosocial ideals that are known to engage members of underrepresented groups more than independent, winner-takes-all approaches. We find that open science has a more connected, collaborative structure than does reproducibility. Semantic analyses of paper abstracts reveal that these literatures have adopted different cultural frames: open science includes more explicitly communal and prosocial language than does reproducibility. Finally, consistent with literature suggesting the diversity benefits of communal and prosocial purposes, we find that women publish more frequently in high-status author positions (first or last) within open science (vs. reproducibility). Furthermore, this finding is further patterned by team size and time. Women are more represented in larger teams within reproducibility, and women's participation is increasing in open science over time and decreasing in reproducibility. We conclude with actionable suggestions for cultivating a more prosocial and diverse culture of science.

Trusting relationships between patients with non-curative cancer and healthcare professionals create ethical obstacles for informed consent in clinical trials: a grounded theory study.

BACKGROUND: Clinical trial participation for patients with non-curative cancer is unlikely to present personal clinical benefit, which raises the bar for informed consent. Previous work demonstrates that decisions by patients in this setting are made within a 'trusting relationship' with healthcare professionals. The current study aimed to further illuminate the nuances of this relationship from both the patients' and healthcare professionals' perspectives. METHODS: Face-to-face interviews using a grounded theory approach were conducted at a regional Cancer Centre in the United Kingdom. Interviews were performed with 34 participants (patients with non-curative cancer, number (n) = 16; healthcare professionals involved in the consent process, n = 18). Data analysis was performed after each interview using open, selective, and theoretical coding. RESULTS: The 'Trusting relationship' with healthcare professionals underpinned patient motivation to participate, with many patients 'feeling lucky' and articulating an unrealistic hope that a clinical trial could provide a cure. Patients adopted the attitude of 'What the doctor thinks is best' and placed significant trust in healthcare professionals, focusing on mainly positive aspects of the information provided. Healthcare professionals recognised that trial information was not received neutrally by patients, with some expressing concerns that patients would consent to 'please' them. This raises the question: Within the trusting relationship between patients and healthcare professionals, 'Is it possible to provide balanced information?'. The theoretical model identified in this study is central to understanding how the trusting professional-patient relationship influences the decision-making process. CONCLUSION: The significant trust placed on healthcare professionals by patients presented an obstacle to delivering balanced trial information, with patients sometimes participating to please the 'experts'. In this high-stakes scenario, it may be pertinent to consider strategies, such as separation of the clinician-researcher roles and enabling patients to articulate their care priorities and preferences within the informed consent process. Further research is needed to expand on these ethical conundrums and ensure patient choice and autonomy in trial participation are prioritised, particularly when the patient's life is limited.

Teacher Mindsets Help Explain Where a Growth-Mindset Intervention Does and Doesn't Work.

A growth-mindset intervention teaches the belief that intellectual abilities can be developed. Where does the intervention work best? Prior research examined school-level moderators using data from the National Study of Learning Mindsets (NSLM), which delivered a short growth-mindset intervention during the first year of high school. In the present research, we used data from the NSLM to examine moderation by teachers' mindsets and answer a new question: Can students independently implement their growth mindsets in virtually any classroom culture, or must students' growth mindsets be supported by their teacher's own growth mindsets (i.e., the mindset-plus-supportive-context hypothesis)? The present analysis (9,167 student records matched with 223 math teachers) supported the latter hypothesis. This result stood up to potentially confounding teacher factors and to a conservative Bayesian analysis. Thus, sustaining growth-mindset effects may require contextual supports that allow the proffered beliefs to take root and flourish.

Healthy U.S.-style dietary patterns can be modified to provide increased energy from protein.

BACKGROUND: Dietary patterns developed by the USDA provide modest levels of protein (14-18% energy) within the Acceptable Macronutrient Distribution Range (AMDR) of 10-35% for adults, though diets providing a higher percentage of energy may be beneficial for some individuals. The purpose of this study was to determine if it is feasible to modify the Healthy U.S.-Style Eating Pattern ("HEP") to provide a higher percentage of energy from protein. METHODS: Using the framework implemented by the USDA in developing the HEP, energy from protein was set at 20%, 25%, and 30%. Amounts of protein foods were proportionally increased while amounts of other foods were adjusted iteratively within specified parameters. The models also disaggregated total meat/poultry into fresh and processed forms to develop patterns maintaining current proportions, current levels, reduced, or no processed meat/poultry. Nutrient intakes were compared with nutrient goals for representative U.S. populations with 2,000 kcal needs (females 19-30 years, males 51-70 years), with 90% of the Recommended Dietary Allowance or Adequate Intake regarded as sufficient. RESULTS: Dietary patterns with 20% energy from protein were constructed with minor deviations from the current 2,000 kcal HEP. Dietary patterns with 25% energy from protein were constructed for all levels of processed meat/poultry excluding the current proportion model, though relative to the current HEP the constructed patterns reflect substantial reductions in amounts of refined grains and starchy vegetables, and substantial increases in protein foods consumed as beans and peas, seafood, and soy products. It was not possible to develop a pattern with 30% energy from protein without reducing the percentage of energy from carbohydrate below the AMDR or non-compliance with other modeling constraints. Stepwise reductions in processed meat/poultry reduced sodium intake. CONCLUSIONS: It is feasible to develop dietary patterns in a 2,000 kcal diet while mirroring the HEP that meet recommended intakes of nutrients with 20% or 25% energy from protein, though the pattern with 25% energy from protein may be more idealistic than realistic. Reduced levels of processed meat/poultry may translate to lower sodium intake.

International Women in Neurosurgery.

The history of women in neurosurgery worldwide has been characterized by adversity and hardships in a male-dominated field, where resilient, tenacious, and ingenious women have nevertheless left their mark. The first women in neurosurgery appeared in Europe at the end of the 1920s, and since then have emerged in all continents in the world. Women neurosurgeons all over the globe have advanced the field in numerous directions, introducing neurosurgical subspecialties to their countries, making scientific and technical advances, and dedicating themselves to humanitarian causes, to name a few. The past 30 years, in particular, have been a period of increasing involvement and responsibility for women in neurosurgery. We must now focus on continual system improvements that will promote a diverse and talented workforce, building a welcoming environment for all aspiring neurosurgeons, in order to advance the specialty in the service of neurosurgical patients.

Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Diversity or representation? Sufficient factors for Black Americans' identity safety during interracial interactions.

OBJECTIVE: Interracial interactions are often fraught with concerns about experiencing discrimination or being negatively stereotyped (i.e., social identity threat). Past research revealed that Black participants interacting with a White partner view the presence of racial diversity in a White partner's friendship network as a signal of identity safety. We extend this work by clarifying the role of ingroup representation in friendship diversity. Namely, we assess social identity safety of Black participants when anticipating an interaction with a White partner whose friendship networks include diversity with or without ingroup representation. METHOD: In an experimental study (N = 301), Black adults (52.8% female, 47.2% male; Mage = 29.96) expected to interact with a White partner who had all White friends (No Diversity); Black and White friends (Diversity with Ingroup Representation); or Asian, Latinx, and White friends (Diversity without Ingroup Representation). We assessed participants' perceptions of their White partner as prejudiced, how they expected their partner would think of them (Black metastereotypes), and their anticipated interaction challenges, rejection concerns, and friendship interest immediately prior to the anticipated interaction. RESULTS: Black participants had fewer anticipated challenges, fewer rejection concerns, and more friendship interest when their White partner's friendship networks included (vs. excluded) ingroup representation. These effects were mediated by perceived partner prejudice and Black metastereotypes. CONCLUSIONS: These findings suggest that while any diversity of an outgroup member's friendship network is better than no diversity, ingroup representation is especially important in reducing threat and increasing social identity safety in interracial interactions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Adequacy of total usual micronutrient intakes among pregnant women in the United States by level of dairy consumption, NHANES 2003-2016.

Background: Dairy products are a rich source of nutrients of public health concern, though most women do not meet the recommended intake of 3 cup-eq/day. Aim: The objective of this analysis was to examine micronutrient adequacy among pregnant women in the US by level of dairy consumption. Methods: Pregnant women (n = 791) ages 20-44 years in NHANES 2003-2016 were categorized by level of dairy consumption (<1, 1 to <2, 2 to <3, and ≥3 cup-eq/day). Usual micronutrient intakes and prevalence of intakes below the Estimated Average Requirement (EAR) or above the Adequate Intake level (AI) were calculated from food alone and food plus dietary supplements using the National Cancer Institute method. Diet quality was assessed with the Healthy Eating Index 2015 (HEI-2015). Results: Pregnant women consuming ≥3 cup-eq/day of dairy were more likely to meet the potassium AI than women consuming lower levels. Compared to women consuming ≥3 cup-eq/day of dairy, women consuming <1 or 1 to <2 cup-eq/day were more likely to have inadequate intake of vitamin D, magnesium, zinc, and vitamin A from foods plus supplements. Compared to women consuming ≥3 cup-eq/day of dairy, women consuming <1 cup-eq/day were more likely to have inadequate intake of calcium and riboflavin. The median urinary iodine concentration (UIC) among pregnant women consuming ≥3 cup-eq/day of dairy was 220 ng/mL compared with median UICs of 98-135 mg/mL among women consuming the lowest levels. Pregnant women consuming ≥3 cup-eq/day of dairy had the highest intake of sodium (mg/day) and saturated fat intake evaluated as a HEI-2015 component. Conclusions: Consumption of recommended levels of dairy products may help pregnant women achieve adequate intakes of select micronutrients.

Fungi populate deep-sea coral gardens as well as marine sediments in the Irish Atlantic Ocean.

Fungi populate deep Oceans in extreme habitats characterized by high hydrostatic pressure, low temperature and absence of sunlight. Marine fungi are potential major contributors to biogeochemical events, critical for marine communities and food web equilibrium under climate change conditions and a valuable source of novel extremozymes and small molecules. Despite their ecophysiological and biotechnological relevance, fungal deep-sea biodiversity has not yet been thoroughly characterized. In this study, we describe the culturable mycobiota associated with the deepest margin of the European Western Continental Shelf: sediments sampled at the Porcupine Bank and deep-water corals and sponges sampled in the Whittard Canyon. Eighty-seven strains were isolated, belonging to 43 taxa and mainly Ascomycota. Ten species and four genera were detected for the first time in the marine environment and a possible new species of Arachnomyces was isolated from sediments. The genera Cladosporium and Penicillium were the most frequent and detected on both substrates, followed by Candida and Emericellopsis. Our results showed two different fungal communities: sediment-associated taxa which were predominantly saprotrophic and animal-associated taxa which were predominantly symbiotic. This survey supports selective fungal biodiversity in the deep North Atlantic, encouraging further mycological studies on cold water coral gardens, often overexploited marine habitats.

Response to the COVID-19 Pandemic Among Posthospital Brain Injury Rehabilitation Providers.

Rehabilitation after significant acquired brain injury (ABI) to address complex independent activities of daily living and return to family and community life is offered primarily after initial hospitalization in outpatient day treatment, group home, skilled nursing, and residential settings and in the home and community of the person served. The coronavirus 2019 pandemic threatened access to care and the health and safety of staff, persons served, and families in these settings. This article describes steps taken to contain this threat by 7 leading posthospital ABI rehabilitation organizations. Outpatient and day treatment facilities were temporarily suspended. In other settings, procedures for isolation, transportation, cleaning, exposure control, infection control, and use of personal protective equipment (PPE) were reinforced with staff. Visitation and community activities were restricted. Staff and others required to enter facilities were screened with symptom checklists and temperature checks. Individuals showing symptoms of infection were quarantined and tested, as possible. New admissions were carefully screened for infection and often initially quarantined. Telehealth played a major role in reducing direct interpersonal contact while continuing to provide services both to outpatients and within facilities. Salary, benefits, training, and managerial support were enhanced for staff. Despite early outbreaks, these procedures were generally effective, with preliminary initial infections rates of only 1.1% for persons served and 2.1% for staff. Reductions in admissions, services, and unanticipated expenses (eg, PPE, more frequent and thorough cleaning) had a major negative financial effect. Providers continue to be challenged to adapt rehabilitative approaches and to reopen services.

Extraordinary claims, extraordinary evidence? A discussion.

Roberts (2020, Learning & Behavior, 48[2], 191-192) discussed research claiming honeybees can do arithmetic. Some readers of this research might regard such claims as unlikely. The present authors used this example as a basis for a debate on the criterion that ought to be used for publication of results or conclusions that could be viewed as unlikely by a significant number of readers, editors, or reviewers.

Adverse intraoperative events during surgical repair of ruptured cerebral aneurysms: a systematic review.

Compared with endovascular techniques, clipping of ruptured cerebral aneurysms has been shown to associate with increased morbidity in several studies. Despite this, clipping remains the preferred option for many aneurysms. The objective of this study is to describe the reported adverse events of open repair of ruptured cerebral aneurysms and their impact on patient outcome. The PubMed, Embase and Cochrane databases were searched between June 1999 and June 2019 to identify original studies of at least 100 patients undergoing surgical repair of ruptured cerebral aneurysms and in which adverse event rates were reported. Thirty-six studies reporting adverse events in a total of 12,410 operations for repair of ruptured cerebral aneurysms were included. Surgical adverse events were common with 36 event types reported including intraoperative rupture (median rate of 16.6%), arterial injury (median rate of 3.8%) and brain swelling (median rate 5.6%). Only 6 surgical events were statistically shown to associate with poor outcomes by any author and for intraoperative rupture (the most frequently analysed), there was an even split between authors finding a statistical association with poor outcome and those finding no association. Even with modern surgical techniques, the technical demands of surgical aneurysm repair continue to lead to a high rate of intraoperative adverse events. Despite this, it is not known which of these intraoperative events are the most important contributors to the poor outcomes often seen in these patients. More research directed towards identifying the events that most drive operative morbidity has the potential to improve outcomes for these patients.

Learning goals mitigate identity threat for Black individuals in threatening interracial interactions.

OBJECTIVE: Interactions between members of different racial and ethnic groups are often stressful. These interactions are stressful, in part, because they contribute to social identity threat-the fear of being judged or treated negatively based on one's social group membership. Previous work separately suggests that the diversity of an interaction partner's friendship network and the goals that people set for themselves influence social identity threat. Bringing these two bodies of work together, the present research examines whether adopting a learning (vs. performance) goal mitigates identity threat for Black people anticipating an interaction with a White partner who had a racially homogenous (vs. diverse) friendship network (a context previously shown to arouse identity threat). METHOD: Two experimental studies (N = 310) were conducted. Black adults (Mage = 29.66, 64% women) primed with either a performance or learning goal anticipated an interaction with a White partner who had either a racially diverse (Study 1) or racially homogenous (Studies 1 and 2) friendship network. After, we assessed participants' social identity threat and anticipated interaction experiences. RESULTS: Black adults primed with learning (vs. performance) goals expected to be perceived more positively by their interaction partner and expected to have more positive interaction experiences when they anticipated an interaction with a White partner who had a racially homogenous network of friends. CONCLUSIONS: These findings suggest that learning goals can mitigate threat among Black individuals within an otherwise identity-threatening interaction context, thus opening the door for positive interracial contact in the future even in the context of challenging interracial interactions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Are Functionally and Genetically Different From Bone Marrow-Derived Mesenchymal Stromal Cells.

There has been considerable interest in the generation of functional mesenchymal stromal cell (MSC) preparations from induced pluripotent stem cells (iPSCs) and this is now regarded as a potential source of unlimited, standardized, high-quality cells for therapeutic applications in regenerative medicine. Although iMSCs meet minimal criteria for defining MSCs in terms of marker expression, there are substantial differences in terms of trilineage potential, specifically a marked reduction in chondrogenic and adipogenic propensity in iMSCs compared with bone marrow-derived (BM) MSCs. To reveal the cellular basis underlying these differences, we conducted phenotypic, functional, and genetic comparisons between iMSCs and BM-MSCs. We found that iMSCs express very high levels of both KDR and MSX2 compared with BM-MSCs. In addition, BM-MSCs had significantly higher levels of PDGFRα. These distinct gene expression profiles were maintained during culture expansion, suggesting that prepared iMSCs are more closely related to vascular progenitor cells (VPCs). Although VPCs can differentiate along the chondrogenic, osteogenic, and adipogenic pathways, they require different inductive conditions compared with BM-MSCs. These observations suggest to us that iMSCs, based on current widely used preparation protocols, do not represent a true alternative to primary MSCs isolated from BM. Furthermore, this study highlights the fact that high levels of expression of typical MSC markers such as CD73, CD90, and CD105 are insufficient to distinguish MSCs from other mesodermal progenitors in differentiated induced pluripotent stem cell cultures. Stem Cells 2019;37:754-765.

A Novel High-Throughput Screening Platform Identifies Itaconate Derivatives from Marine Penicillium antarcticum as Inhibitors of Mesenchymal Stem Cell Differentiation.

Worldwide diffused diseases such as osteoarthritis, atherosclerosis or chronic kidney disease are associated with a tissue calcification process which may involve unexpected local stem cell differentiation. Current pharmacological treatments for such musculoskeletal conditions are weakly effective, sometimes extremely expensive and often absent. The potential to develop new therapies is represented by the discovery of small molecules modulating resident progenitor cell differentiation to prevent aberrant tissue calcification. The marine environment is a rich reserve of compounds with pharmaceutical potential and many novel molecules are isolated from macro and microorganisms annually. The potential of small molecules synthetized by marine filamentous fungi to influence the osteogenic and chondrogenic differentiation of human mesenchymal stem/stromal cells (hMSCs) was investigated using a novel, high-throughput automated screening platform. Metabolites synthetized by the marine-derived fungus Penicillium antarcticum were evaluated on the platform. Itaconic acid derivatives were identified as inhibitors of calcium elaboration into the matrix of osteogenically differentiated hMSCs and also inhibited hMSC chondrogenic differentiation, highlighting their capacity to impair ectopic calcification. Bioactive small molecule discovery is critical to address ectopic tissue calcification and the use of biologically relevant assays to identify naturally occurring metabolites from marine sources represents a strategy that can contribute to this effort.

Nothing to lose: a grounded theory study of patients' and healthcare professionals' perspectives of being involved in the consent process for oncology trials with non-curative intent.

BACKGROUND: Clinical cancer research trials may offer little or no direct clinical benefit to participants where a cure is no longer possible. As such, the decision-making and consent process for patient participation is often challenging. AIM: To gain understanding of how patients make decisions regarding clinical trial participation, from the perspective of both the patient and healthcare professionals involved. METHODS: In-depth, face to face interviews using a grounded theory approach. This study was conducted in a regional Cancer Centre in the United Kingdom. Of the 36 interviews, 16 were conducted with patients with cancer that had non-curative intent and 18 with healthcare professionals involved in the consent process. RESULTS: 'Nothing to lose' was identified as the core category that underpinned all other data within the study. This highlighted the desperation articulated by participants, who asserted trial participation was the 'only hope in the room'. The decision regarding participation was taken within a 'trusting relationship' that was important to both patients and professionals. Both were united in their 'fight against cancer'. These two categories are critical in understanding the decision-making/consent process and are supported by other themes presented in the theoretical model. CONCLUSION: This study presents an important insight into the complex and ethically contentious situation of consent in clinical trials that have non-curative intent. It confirms that patients with limited options trust their doctor and frequently hold unrealistic hopes for personal benefit. It highlights a need for further research to develop a more robust and context appropriate consent process.