Gatekeeper Role Research Articles

Abstract IA016: Vascular control of metastasis

Abstract The molecular analysis of tumor vessel interactions during tumor progression and metastasis has primarily focused on the study of tumor cell-derived angiogenic and lymphangiogenic signals with the purpose to exploit such factors as therapeutic targets. Angiogenic factors activate endothelial cells in nearby blood and lymphatic capillaries to sprout towards the tumor. Tumor angiogenesis thereby not only nourishes the growing tumor, but access to the blood and lymphatic vasculatures enables cells from the primary tumor to enter the circulation to eventually form metastases at distant sites. The complex cellular interactions between tumor cells and endothelial cells have in this context mostly been studied from a tumor cell-centric perspective, i.e., the tumor cells send signals to which endothelial cells merely respond. Yet, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines but exerts active ’angiocrine’ gatekeeper roles controlling their microenvironment in an instructive manner. We have applied the concepts of angiocrine signaling towards the study of tumor progression and metastasis. Employing novel surgical preclinical metastasis models that better mimic tumor progression and the response to therapy as it occurs in humans, we have molecularly dissected vascular endothelial cells in progressing primary tumors as well as in the pre-metastatic and metastatic niches. These experiments were on the one hand aimed at establishing the systems map of endothelial transcriptomic changes during tumor progression and metastasis and on the other hand to identify and validate novel therapeutic targets. This presentation will review recent advances in the field of tumor microenvironment research and present novel angiocrine signaling mechanisms as promising targets of future mechanism-driven anti-metastatic therapy. Citation Format: Hellmut G. Augustin. Vascular control of metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA016.

The mediating role of psychological functioning and maternal gatekeeping in the relationship of work-family conflict and gender roles with co-parenting

The mediating role of psychological functioning and maternal gatekeeping in the relationship of work-family conflict and gender roles with co-parenting

Participation of persons living with dementia in research: A means to address epistemic injustice.

Epistemic injustice refers to wronging or mistreating individuals in terms of their capacity as knowers, based on prejudices or negative attitudes. Excluding people with dementia from research is a form of epistemic injustice. In this article, we discuss epistemic injustice associated with data collection processes and the participation of people with dementia in scientific research. The challenges of participation that we discuss pertain to the role of gatekeepers and ethical research perspectives. The arguments presented are based on previous research, experiences from our current project, and critical self-assessment regarding the latter. The aim is to shed light on what enables or prevents people living with dementia from participating in research, and how this is connected to epistemic injustice. It is known that prejudices related to dementia affect both researchers and people living with dementia: the former tend to exclude people with dementia, and the latter may practice self-silencing due to dementia-related stigma. In addition to these individual issues, we argue that epistemic injustice occurs at a structural level, where a major role is played by gatekeepers and research ethics panels. As close family members, health officials, and dementia-related associations are the main gatekeepers, their attitudes and perceptions are highlighted. In terms of ethical issues, the concept of informed consent needs to be elaborated. If the research is not expected to harm participants and may contribute to improving the lives of those with dementia, the perspective should be shifted from informed consent to ongoing consent assessment. While acknowledging the features and symptoms of dementia, researchers should be more courageous, trust in the good cause, and enable persons living with dementia to participate in research that concerns them. This is the only way for researchers to genuinely understand the social world, experiences, and needs of those with dementia and to address epistemic injustice.

Changing Roles of Gatekeepers in the Era of New Media: A Study of Gatekeeping on Instagram

Changing Roles of Gatekeepers in the Era of New Media: A Study of Gatekeeping on Instagram

Capacity, Autonomy, and Risk: Reflecting on Asymmetries in Capacity to Consent and Capacity to Refuse

AbstractThere has been renewed interest in whether we should understand standards of decision-making capacity (DMC) to be risk-relative. Critics of risk-relative standards often highlight a puzzling asymmetry that they imply; a patient may have the requisite DMC to consent to a treatment that is in their best interests, whilst lacking the requisite DMC to refuse that same treatment, given the much higher risk that this would entail. Whilst some have argued that this asymmetry suggests that risk-relative standards are nonsensical, in this paper I defend a ‘quality of evidence’ view of such standards. I begin by outlining DMC’s purported gate-keeping role in medical ethics, and identifying three key normative claims that undergird this role. I then explain how two competing theories of risk-relative standards are incompatible with at least one of these claims. Drawing on Douglas’ distinction between standards of ‘true capacity’ and standards invoked in the ‘test’ for capacity, I then outline my ‘quality of evidence’ view. I explain how the view is compatible with the aforementioned normative claims, and outline the nature of the asymmetry it implies. I conclude by responding to the objection that there is no meaningful distinction between ‘true capacity’ and the ‘test’ for capacity.

Changes in attitudes toward suicide after brief gatekeeper education: Findings from population-based repeated cross-sectional surveys conducted among middle-aged and older adults

Objective This study aimed to investigate changes in attitudes toward suicide following a universal home visitation program that included a brief face-to-face educational session focusing on gatekeeper roles in Japan.Methods Between 2015 and 2017, members of 169 households in an intervention district from a northern Japanese township were invited to attend an educational session during home visits. The participation rate was 72.8%, with 94.5% of the participants aged over 40. Repeated cross-sectional population-based surveys were conducted among adults in the towns in 2015 and 2021. Data from the surveys, focusing on individuals aged 40-79 years and residing in the intervention and matched control districts (where no visits occurred and only information was distributed through leaflets), were used to assess the prevalence of self-reported views toward suicide. The self-reported views encompassed "no substantial thoughts," "inevitable," "shameful," "annoying," "tragic," "must be managed," and "romantic" in addition to personal and perceived stigma, depressive symptoms (assessed using the Kessler Psychological Distress Scale-6), and suicidal ideation. Data were analyzed using generalized linear mixed models. The Cochran-Armitage test was used to analyze linear trends in the proportion of views that exhibited changes.Results Participation rates were 61.8% (n ＝ 357) in 2015 and 52.8% (n ＝ 257) in 2021. The intervention group showed a significant difference in the prevalence of the "inevitable" view between baseline and 4-year follow-up (P ＝ 0.026). Marginal pre-post differences were observed among the two types of stigma; however, the symptoms remained unchanged. A marginally significant difference in the change of the "inevitable" view was observed between the two groups. In the follow-up, more knowledgeable respondents in the intervention group were less likely to view suicide as "inevitable," a trend not seen in the control group.Conclusions The universal home visitation program, including a face-to-face session focusing on the gatekeeper role, was associated with a decreased prevalence of the "inevitable" attitude between the baseline and 4-year follow-up among community-dwelling adults aged 40-79. This suggests that face-to-face interactions with healthcare professionals can reduce the tendency to condone suicide among middle-aged and older adults in community settings.

Contested role boundaries and professional title: Implications of the independent review of podiatric surgery in Australia.

In October 2023, the Podiatry Board of Australia commissioned an independent review of the regulation of podiatric surgery in Australia, with a remit to re-evaluate the regulatory framework, identify any risks to patient safety and recommend improvements to public protection. It reported in March 2024 and set out 14 key recommendations. The review was prompted by a number of complaints about podiatric surgeons but also reflected calls for reform by the medical profession and several critical media reports. This paper sets out to examine the review report, alongside the concerns of the medical profession and the media articles expressed within it, through the lens of an established sociological framework focused on interprofessional conflict and the contested use of professional titles. As a review rather than the research paper, the Independent Review of Podiatric Surgery (the 'Paterson Report') served as data for the sociological analysis, adopting a Neo-Weberian and Bordieuan framework to examine the strategies adopted by the medical profession and media reports cited in the report, consistent with the exercise of professional power. The sociological analysis provides insights into the ways in which professions seek to maintain symbolic, social, cultural and economic privileges and rewards through the exclusion of competitors, using strategies such as social closure, symbolic violence, symbolic devaluation, gatekeeper roles, and jurisdictional disputes. The review report acknowledges the influence of the medical profession and its opposition to the practice of podiatric surgery and use of the title 'podiatric surgeon'. The arguments made and strategies deployed are consistent with those found in the wider literature. In light of these findings, the implications for the future of podiatric surgery are considered in terms of professional practice, use of professional title, and access to public funding.

게이트키퍼 역할을 하는 수퍼바이저의 내러티브 탐구

Objectives This study was conducted to find out what is experienced in the role of a gatekeeper and what it means. Methods For this purpose, three supervisors with 10 to 30 years of counseling experience were selected as participants, and data were collected through in-depth interviews. Based on the collected data, the narrative research method proposed by Clandinin and Connelly was used to understand the participants' vivid experiences and reveal their meaning. In addition, to improve the quality of the research, the research was conducted under the supervision of a reviewer. Results Looking at the experiences of the supervisors' gatekeepers, I found that although they had never been taught the role of gatekeeper, they each fulfilled the role in their own way. In this process, they came to feel that they had responsibility as gatekeepers but no authority, and as their responsibility increased, they began to experience confusion and doubt about whether their judgments and decisions were correct. Therefore, it is emphasized that what is more important than teaching well is to check oneself as a gatekeeper. Conclusions Through research, the importance and necessity of the gatekeeper role was confirmed. It also suggests that self-understanding is necessary to play the role of gatekeeper. Lastly, the significance of the study can be attributed to the fact that it laid the foundation for research into the detailed field of gatekeepers.

Microbial Gatekeepers of Fertility in the Female Reproductive Microbiome of Cattle.

This review paper delves into the intricate relationship between the genital microbiome and fertility outcomes in livestock, with a specific focus on cattle. Drawing upon insights derived from culture-independent metagenomics studies, the paper meticulously examines the composition and dynamics of the genital microbiome. Through advanced techniques such as high-throughput sequencing, the review illuminates the temporal shifts in microbial communities and their profound implications for reproductive health. The analysis underscores the association between dysbiosis-an imbalance in microbial communities-and the development of reproductive diseases, shedding light on the pivotal role of microbial gatekeepers in livestock fertility. Furthermore, the paper emphasizes the need for continued exploration of uncharted dimensions of the female reproductive microbiome to unlock new insights into its impact on fertility. By elucidating the complex interplay between microbial communities and reproductive health, this review underscores the importance of innovative strategies aimed at enhancing fertility and mitigating reproductive diseases in livestock populations.

How general practitioners in France are coping with increased healthcare demand and physician shortages. A panel data survey and hierarchical clustering

BackgroundGeneral practitioners (GPs) face quantitative and qualitative changes in patient demand and doctor shortages. ObjectivesTo investigate how GPs cope with doctor shortage issues. Materials and methodsTwo cross-sectional surveys of a representative panel of 1530 GPs in 2019 and 2022 about their perceptions of physician shortages, working hours worked (WHW), and adaptive behaviors. Hierarchical clustering enabled identification of profiles with different adaptation patterns. Multiple Poisson or logistic regression models studied associations between GPs’ profiles and professional characteristics. Results87.4 % of GPs applied at least one adaptation to control patients’ healthcare demand. 24 % adopted task-shifting while their average WHW decreased by 3.6 h between 2019 and 2022. Four GP profiles were identified. “Low adapters/low workload” and “Low adapters/high workload” (25 % of the sample each) reported 2.4 adaptive measures: 75.5 % refused to be new patients' preferred doctor in the former group (vs 5.1 %). “High adapters/unchanged consultations” (30.7 %) and “High adapters/shortened consultations” (18.9 %) reported 4.8 and 6.1 adaptations, respectively. They were more likely to practice in medically underserved areas. ConclusionThese results call into question GPs’ gatekeeper role in the French healthcare system. Moreover, the marked reduction in WHW in underserved areas is likely to exacerbate their uneven distribution nationwide. Encouraging vertical integration between HCPs while enhancing cooperation and task-shifting is probably a pathway toward improving the relative GP shortage.

Black Robes and White Coats: Daubert Standard and Medical and Legal Considerations for Medical Expert Witnesses.

Expert testimony can play a pivotal role in a legal case involving a medical issue, but it is crucial that this testimony be scientifically sound. In the United States, the Frye Standard demanded that such expert medical testimony be "generally accepted," but it has been superseded by the more demanding Daubert Standard. Under Daubert, judges became "gatekeepers" as to what scientific material was admissible in court and what might be dismissed as junk science. While a vast improvement over Frye, the Daubert Standard still faces its own problems. Judges usually lack scientific and medical expertise and sometimes have to do their own medical research to be able to evaluate the experts and their testimony. Expert witnesses can be subjected to an adversarial Daubert challenge, even during trial, to establish their credentials and the evidence they are reporting. About half of all judges have had no formal education in handling scientific evidence, but 91% felt comfortable in their gatekeeper role. Considerations for expert witnesses include training or coaching, familiarity with the entire case and courtroom procedures, and an ability to not just know the evidence but to be able to communicate it effectively to a lay audience (jury). Some countries have pioneered a concurrent testimony approach in complex cases, whereby experts argue the evidence of the case under oath before a judge in advance of the trial to determine where there are points of agreement and where the main areas of contention reside. This process, colorfully called "hot tubbing," is aimed at a more conciliatory approach to reaching compromises. Nevertheless, bias still can result even in hot-tubbing cases, and more research is needed to better understand the nature of jury bias and how it can affect jury decisions in complex medical cases.

Reshaping the Spheres: Gatekeeping as an Ethical Normative Imperative

ABSTRACT This theoretical essay argues for reconstituting the normative role of gatekeeping of journalism in a functioning democracy. It contends that in this time of disinformation, misinformation and fake news, the journalist’s main normative role should involve gatekeeping all deviant information from the mainstream public sphere. It then articulates why the space inside the sphere of legitimate controversy grew in recent years, and journalists, through gatekeeping, must restore it to its normative ideal.

Between a rock and a hard place: A geosocial approach to water insecurity in Kabul

Approximately 50% of the global population currently experiences severe water scarcity, a situation likely to intensify due to climate change. At the same time, the poorest population segments bear the greatest burden of water insecurity. This intersection of geophysical, geochemical, and socio-economic dimensions of water (in)security challenges requires a geosocial perspective, one that attends simultaneously to geophysical, geochemical, and socio-economic dimensions. Our qualitative study, conducted through 68 semi-structured interviews across two distinct sub-basins in Kabul, revealed disparities in groundwater levels, water quality, water prices, and lived experiences of water insecurity. While environmental stressors like drought and groundwater contamination contribute to water insecurity, socio-economic factors such as gender and property ownership exacerbate these impacts: Women and children bear a heavy burden of securing water, with children’s involvement in water-fetching leading to instances of violence. Furthermore, trucked water costs 33 times that of piped water, echoing alarming global trends where less privileged communities endure disproportionately greater challenges of water inaccessibility. We outline policy implications for monitoring groundwater abstraction and underscore the need for tailored strategies to combat water scarcity, such as pro-poor water strategies. Additionally, our work draws attention to the role of local gatekeepers who have informally regulated water usage in response to drought-induced scarcity, particularly in the absence of functioning government policies, underscoring the importance of collaboration with local stakeholders to ensure sustainable access to water. We argue that a geosocial approach to water (in)security can provide high-resolution findings and reveal critical gaps between common metrics and the realities of water (in)security, which also underlines the need for integrated approaches incorporating both quantitative and qualitative research.

Our gateway is your gatekeeper: benefits and constraints of EMI for different participants in Japanese ELF contexts

Abstract This paper explores the interconnectedness of gatekeeper and gateway roles the same English-medium instruction (EMI) policy plays for different student populations at different times. The research site is located in an EMI programme at a Japanese university, where, for international students, EMI opens a gateway to the university, Japanese ability not being required at the entry point, whereas the same policy plays a gatekeeping role for Japanese students, a high English proficiency level based on native English speaker (NES) norms being required. However, for international students with plans to work for Japanese companies after graduation, their low Japanese ability starts playing a gatekeeping role for their future career, contrary to the situation at the outset. In contrast, Japanese students, who initially struggle to get used to EMI, after a few years, become empowered by their ability to use English as a lingua franca (ELF), which becomes a gateway to new career opportunities. Thus, the same EMI policy could play opposing roles for different student populations at different times, a gateway turning gatekeeper for one group, while for another, the initial gatekeeper turning gateway after some time. The exploration is mostly based on our interview data with EMI graduates at both undergraduate and graduate levels. Implications for language policy will also be discussed.

Algorithmic orientalism? Netflix’s representation of China in Brazil

For decades, the geopolitical domination of the United States remained almost unquestioned. However, other countries have emerged as poles of influence in recent years, including China and Brazil. Despite this, cultural and media interaction between the two countries is still limited and often mediated by the United States. This paper explores the algorithmic representation of China by the video streaming platform Netflix and argues that the company acts imperialistically by seeking to establish monopolistic control of the global Internet television market and promoting biases that we call ‘algorithmic orientalism’. By presenting China to the Brazilian public through this lens, Netflix plays the role of cultural gatekeeper that continues to promote hegemonically American worldviews.

Detection of cardiac amyloidosis on routine bone scintigraphy: an important gatekeeper role for the nuclear medicine physician

Cardiac amyloidosis (CA)—mostly transthyretin-related (ATTR-CA)—has recently gained interest in cardiology. Bone scintigraphy (BS) is one of the main screening tools for ATTR-CA but also used for various other reasons. The objective was to evaluate whether all CA cases are detected and what happens during follow-up. All routine BS performed at the Maastricht University Medical Center (May 2012–August 2020) were screened for the presence of CA. Scans performed for suspected CA were excluded. A Perugini stage ≥1 was classified as positive necessitating further examination. The electronic medical record system was evaluated for any contact with cardiology or other specialists until 2021. Of the 2738 BS evaluated, 40 scans (1.46%; median age 73.5 [IQR: 65.8–79.5], 82.5% male) were positive (Perugini grade 1: 31/77.5%, grade 2: 6/15%, grade 3: 3/7.5%); the potential diagnosis ATTR-CA was not seen in 38 patients (95%) by the nuclear medicine specialist. During follow-up, 19 out of those 40 patients (47.5%) underwent cardiac evaluation without diagnosing CA. Available echocardiograms of patients with a positive BS showed left ventricular hypertrophy, a preserved ejection fraction, and diastolic dysfunction ≥2 in 9/47%, 10/53%, and 4/21% of patients, respectively. Additionally, 20 (50%) patients presented to at least one specialty with symptoms indicative of cardiac amyloidosis. The prevalence of a positive BS indicating potential CA in an unselected population is low but substantial. The majority was not detected which asks for better awareness for CA of all involved specialists to ensure appropriate treatment and follow-up.Graphical abstract

Alternative mechanisms of Notch activation by partitioning into distinct endosomal domains.

Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism. This requirement for Deltex is bypassed by the downregulation of ESCRT-III. In contrast, while ESCRT-I depletion also activates Notch, it does so by an ADAM10-dependent/TRPML-independent mechanism and Notch is retained in the lipid raft-like microdomain. In the absence of such endosomal perturbation, different activating Notch mutations also localize to different microdomains and are activated by different mechanisms. Our findings demonstrate the interplay between Notch regulators, endosomal trafficking components, and Notch genetics, which defines membrane locations and activation mechanisms.

Connected health services: Health professionals' role as seen by parents of a child with inflammatory bowel disease.

Connected health services will change the scope of health professionals' roles. It is unclear how parents of a child with inflammatory bowel disease perceive the role of health professionals in relation to these services and what their experiences and needs are. The purpose of this study is to highlight parents' experiences with this role. Furthermore, it aims to outline the fundamental needs that parents have regarding this role, in order to promote audience-specific access to these services and derive overarching action measures. Fourteen parents of children with inflammatory bowel disease from seven different clinics in Switzerland were recruited. Between August 2022 and February 2023, these parents were interviewed in semi-structured interviews. The interviews were analyzed using a structured qualitative content analysis. Five main categories were identified, with few parents having prior experience with the role of health professionals in this area. Parents saw health professionals in the role of gatekeepers, transferers of knowledge and in a supporting function for these services. From the parents' perspective, health professionals should recognize the limitations of these services and use them as a complement to standard treatment. The role of health professionals in relation to connected health services needs to be adapted from the parents' perspective. To meet the needs of parents, health professionals must have access to these services. In addition to health professionals' personal engagement with these services, institutional and policy changes, as well as research on role development from the perspective of other stakeholders are needed.

Multi-omic profiling of breast tumor microenvironment uncovers a role of mitochondrial calcium gatekeepers.

In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach. Unlike previous research, we utilized a novel web application tailored for whole tumor tissue, single-cell, and spatial transcriptomics analysis to investigate the association between MiCU1/2 and the tumor immune microenvironment (TIME). Our gene set enrichment analysis (GSEA) provided insights into the primary biological effects of MiCU1/2, while our CRISPR-based drug screening repository identified potential effective drugs. Our study revealed that high MiCU1/2 expression serves as an independent diagnostic biomarker, correlating with advanced clinical status and indicating poorer recurrence-free survival (RFS) rates in BRCA patients. Additionally, spatial transcriptome analysis highlighted the heightened expression of MiCU1/2 in tumors and its relevance in surrounding immune cells. Furthermore, using the CIBERSORT algorithm, we discovered a positive correlation between MiCU1/2 levels and macrophage infiltration, underscoring their potential impact on immune infiltration. We also identified expression patterns of immune-related genes associated with responses against various immune cell types, including CXCL, MIF, GDF, SPP1, and IL16. Finally, our pharmacogenomic screening identified potential small molecule drugs capable of effectively targeting breast cancer cells with elevated MiCU1/2 expression. Overall, our study establishes MiCU1/2 as a promising novel biomarker for BRCA diagnosis and prognostic prediction, as well as a potential therapeutic target, highlighting the importance of exploring these pathways to advance patient care and outcomes in BRCA treatment.

Dehalococcoides mccartyi strain CBDB1 takes up protons from the cytoplasm to reductively dehalogenate organohalides indicating a new modus of proton motive force generation.

Proton translocation across the cytoplasmic membrane is a vital process for all organisms. Dehalococcoides strains are strictly anaerobic organohalide respiring bacteria that lack quinones and cytochromes but express a large membrane-bound protein complex (OHR complex) proposed to generate a proton gradient. However, its functioning is unclear. By using a dehalogenase-based enzyme activity assay with deuterium-labelled water in various experimental designs, we obtained evidence that the halogen atom of the halogenated electron acceptor is substituted with a proton from the cytoplasm. This suggests that the protein complex couples exergonic electron flux through the periplasmic subunits of the OHR complex to the endergonic transport of protons from the cytoplasm across the cytoplasmic membrane against the proton gradient to the halogenated electron acceptor. Using computational tools, we located two proton-conducting half-channels in the AlphaFold2-predicted structure of the OmeB subunit of the OHR complex, converging in a highly conserved arginine residue that could play a proton gatekeeper role. The cytoplasmic proton half-channel in OmeB is connected to a putative proton-conducting path within the reductive dehalogenase subunit. Our results indicate that the reductive dehalogenase and its halogenated substrate serve as both electron and proton acceptors, providing insights into the proton translocation mechanism within the OHR complex and contributing to a better understanding of energy conservation in D. mccartyi strains. Our results reveal a very simple mode of energy conservation in anaerobic bacteria, showing that proton translocation coupled to periplasmic electron flow might have importance also in other microbial processes and biotechnological applications.