Exclusive Pattern Research Articles

The analysis of BRAF fusions characteristics in Chinese solid tumor patients.

e15073 Background: BRAF encodes a RAF kinase, which signal downstream of RAS and activate the MAPK pathway, and has emerged as a major oncogenic driver and a potential therapy target. BRAF V600E base substitution is an approved target for the BRAF inhibitors in solid tumors. BRAF gene fusions represent a different mechanism of BRAF activation. BRAF fusions have shown responses to MEK inhibitors and non-specific RAF inhibitors (eg, sorafenib) in Melanoma (NCCN). We sought to analysis of BRAF fusions characteristics in Chinese solid tumor patients to explore the possibility of therapeutic intervention in solid tumors. Methods: We comprehensively characterized BRAF fusions from next-generation sequencing (NGS) data from May 2019 to January 2023 in 80083 various solid tumors. Considering the characteristics of the receptor tyrosine kinase, we focused on the BRAF fusions which contain the kinase domain. Results: A total of 164 unique cases (70.1% (115/164) glioma and 29.9% (49/164) non-glioma with BRAF fusions) were identified. The non-glioma cohort consisted up mainly lung tumors (49%, 24/49), colorectal tumors (18.4%, 9/49), pancreatic tumors (10.2%,5/49), melanoma (9.2%, 4/49) and biliary tumors (4.1%, 2/49). In the glioma cohort, the median age of the 115 patients was 12 with a range of 0–66; 43 (37.4%) of the patients were female and 72 (62.6%) were male. On the other hand, the median age was 64 with a range of 33–82; 23 (46.9%) of the patients were female and 26 (53.10%) were male in the non-glioma cohort. In the glioma cohort, 82.4% of the partners were KIAA1549. However, the most common fusion partners were AGK (14.04%), TRIM24(14.0%), SND1(12.28%), TPK1(8.77%) in the non-glioma cohort. These BRAF fusions comprised 49 unique 5′ fusion partners, of which 51% (25) were known and 49.0% (24) were novel. 14 novel partners were TMEM176B, HMBOX1, SEMA3E, LOC441204, PDE4D, DENND2A, STIM1, TNS3, PRRC2B, BCR, MET, COL4A3BP, TPM4, ZBTB16 and 10 novel partners were intergenic region. 130 patients with BRAF fusions could be evaluated for concurrent mutations. Of interest is that no KRAS and BRAF V600E mutations were identified in the 130 cases. Conclusions: BRAF fusions were detected in 0.2% (164/80083) of Chinese solid tumor patients. 70.1% of BRAF fusion positive cases were diagnosed with glioma and 29.9% were diagnosed with non-glioma. 14 novel BRAF fusion partners were discovered. BRAF fusion is an important driver genomic alteration and occur in a mutually exclusive pattern with other activating mutations in the MAP kinase signaling pathway. BRAF fusion targeted therapies should be further explored in solid tumors.

Measuring social exclusion and its distribution in England

BackgroundSocial exclusion is a multidimensional concept referring processes which restrict the ability of individuals or groups to participate fully in society. While social exclusion has been used to explore patterns of disadvantage, it has been difficult to measure. Thus, we aimed to use population-based data to measure social exclusion and its constituent domains and to describe its distribution in England.MethodsWe used data from Understanding Society in 2009/2010 develop a multidimensional measurement approach, replicated in 2018/2019. We defined five domains of social exclusion from the literature and expert consultation: material, relational, political, digital, and structural. In both waves, we identified measures for each domain, then conducted principal component analysis to identify the components. We generated domain scores and an overall social exclusion score. We described the distribution of social exclusion and its domains by sex, region, age, and ethnicity.ResultsWe found the level of social exclusion was higher in the youngest age group and decreased by age. We found elevated levels of overall social exclusion for ethnic minoritised groups including African, Arab, and Caribbean groups compared to White British groups. We found distinct patterns within each domain.DiscussionWe developed an overall measure of social exclusion with five domains, and finding distinct patterns of social exclusion by age, ethnicity, and region which varied across domain. These findings suggest that attention should be paid to the separate domains due to different population distributions. This measurement approach moves beyond conceptual discussions of social exclusion and demonstrates the utility of a quantitative measure of social exclusion for use in health and social research.

Demographic reporting and phenotypic exclusion in fNIRS.

Functional near-infrared spectroscopy (fNIRS) promises to be a leading non-invasive neuroimaging method due to its portability and low cost. However, concerns are rising over its inclusivity of all skin tones and hair types (Parker and Ricard, 2022, Webb et al., 2022). Functional NIRS relies on direct contact of light-emitting optodes to the scalp, which can be blocked more by longer, darker, and especially curlier hair. Additionally, NIR light can be attenuated by melanin, which is accounted for in neither fNIRS hardware nor analysis methods. Recent work has shown that overlooking these considerations in other modalities like EEG leads to the disproportionate exclusion of individuals with these phenotypes-especially Black people-in both clinical and research literature (Choy, 2020; Bradford et al., 2022; Louis et al., 2023). In this article, we sought to determine if (Jöbsis, 1977) biomedical optics developers and researchers report fNIRS performance variability between skin tones and hair textures, (2a) fNIRS neuroscience practitioners report phenotypic and demographic details in their articles, and thus, (2b) is a similar pattern of participant exclusion found in EEG also present in the fNIRS literature. We present a literature review of top Biomedical Optics and Human Neuroscience journals, showing that demographic and phenotypic reporting is unpopular in both fNIRS development and neuroscience applications. We conclude with a list of recommendations to the fNIRS community including examples of Black researchers addressing these issues head-on, inclusive best practices for fNIRS researchers, and recommendations to funding and regulatory bodies to achieve an inclusive neuroscience enterprise in fNIRS and beyond.

UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.

Introduction: Sustainability, Democracy and the Dark Sides of Civil Society

Despite widespread acknowledgement of the value of sustainability, the transition towards more sustainable economies and societies remains a challenge around the world. Civil societies play an important role not only in supporting government efforts on sustainability by ‘filling gaps’ and raising social awareness, but also in pioneering new practices and disrupting particular governmental or corporate strategies, as well as engaging and empowering previously marginalised individuals and groups. Yet civil society is not always a champion of sustainability nor of democracy; these actors may of course also destabilise innovations, depoliticise sustainability issues by reifying certain concepts or approaches and reinforce social hierarchies and patterns of exclusion that can undermine any transformative potential and bolster the unsustainable status quo. This Special Issue is therefore dedicated to interrogating what we see as the ambiguous, yet critical, role played by civil societies in sustainability politics. This introductory paper intends not only to draw attention to some of the arguments, theories and challenges found in each of the individual papers collected here, but also to pull on the common threads that run through them, as well as to unpick some of the different uses of the key terminology that they employ. We aim, moreover, to highlight the inevitable tension between the ‘democratic side’ and the ‘dark side’ of civil society and its politics of sustainability.

Abstract 3300: Development of a diagnostic antibody for anti-BTN1A1 therapy, a novel immune checkpoint inhibitor mutually exclusive of PD-L1/PD-1

Abstract Butyrophilin 1A1 (BTN1A1) is currently undergoing investigation in Phase 1 clinical trials as a novel immune checkpoint protein for the treatment of solid tumors. BTN1A1 exhibits a mutually exclusive expression pattern to that of PD-1/PD-L1, making anti-BTN1A1 antibody therapy an attractive option for cancer patients with PD-L1 refractory or relapsed disease. While current cancer immunotherapies have shown some efficacy against late-stage disease, there remains a major unmet medical need as a large number of patients fail to respond to current treatments. BTN1A1 has been studied at length in preclinical models to characterize its immunomodulatory functions, revealing its ability to inhibit the proliferation of activated T cells and the ability of these cells to kill tumor cells in vitro. In vivo, BTN1A1-overexpressing tumor models exhibit accelerated growth, whereas the growth of BTN1A1-deficient tumors is impaired in immunocompetent settings, supporting a role for this protein in the regulation of immune evasion. Here in, we present the development of a diagnostic antibody for use in the anti-BTN1A1 therapy clinical trials to enable the immunohistochemical (IHC) detection of human BTN1A1. A high-quality BTN1A1 antibody may help predict which patients are more likely to respond to BTN1A1 antibody-based cancer therapy, similar to the PD-L1 companion diagnostic test for anti-PD-L1/PD-1 therapy. The characterization of the developed BTN1A1 antibody was conducted via ELISA, Western blotting, confocal microscopy, and flow cytometry to demonstrate its overall performance. Validation was performed using formalin-fixed paraffin-embedded human tumor tissue samples to determine the analytical sensitivity and specificity of the IHC assay. This antibody was also found to be of value for imaging mass cytometry and flow cytometry experiments elucidating applicable clinical features of both human tumor tissues and immune cells. Specifically, the developed antibody can detect the robust expression of BTN1A1 on both cancer cells and immune cells, while also revealing the mutually exclusive expression of BTN1A1 and PD-L1. Finally, we demonstrate the capability of a BTN1A1 antibody that can be used to identify BTN1A1-positive patients with a high degree of analytical sensitivity and specificity. Citation Format: Stephen S. Yoo. Development of a diagnostic antibody for anti-BTN1A1 therapy, a novel immune checkpoint inhibitor mutually exclusive of PD-L1/PD-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3300.

The Lab as a Classroom: Advancing Faculty Research Through Undergraduate Experiential Education

ABSTRACTBoth undergraduate students and faculty members face a challenging job market that requires innovative approaches to skill development and research products. Moreover, entrenched approaches to research and education reinforce traditional hierarchies, exclusionary norms, and exploitative practices. This article describes a lab-based pedagogical framework designed to support faculty research goals and student learning and, simultaneously, to attenuate patterns of historical exclusion. This approach leverages evidence-based best practices from experiential education, team-based workflows, an understanding of servant leadership, and “whole-person”–style mentorship models. We find that these tools advance faculty research goals (in terms of both quality and productivity), support student learning in ways beyond traditional undergraduate coursework, and disrupt patterns of historical exclusion. We provide qualitative evidence to support our model and discuss the hurdles and challenges still to be overcome.

Common and exclusive spontaneous neural activity patterns underlying pure generalized anxiety disorder and comorbid generalized anxiety disorder and depression

BackgroundThis study aimed to identify common and exclusive neural substrates underlying pure generalized anxiety disorder (GAD, G0) and comorbid GAD and depression (G1), assess whether they could assist in diagnosis and prediction of treatment response, and determine whether comorbid depression in GAD patients would change their neural plasticity. MethodsA longitudinal study was conducted, involving 98 patients (40 in the G0 group and 58 in the G1 group) and 54 healthy controls (HCs). The fractional amplitude of low-frequency fluctuations (fALFF), support vector machine, and support vector regression were employed. ResultsThe shared neural underpinnings across the two subtypes of GAD were hyperactivity in the right cerebellar Crus II and inferior temporal gyrus and hypoactivity in the right postcentral gyrus. The G1 group showed hypoactivity in the frontal gyrus, compared with HCs, and hyperactivity in the middle temporal gyrus, compared with the G0 group or HCs. These alterations could aid in diagnosis and the prediction of treatment response with high accuracy. After treatment, both the G1 and G0 groups showed higher fALFF than those before treatment but were located in different brain regions. LimitationsThe study was performed in a single center and subjects showed a fairly homogeneous ethnicity. ConclusionsCommon and exclusive neural substrates underlying the two subtypes of GAD were identified, which could assist in diagnosis and the prediction of treatment response. Pharmacotherapy for the two subtypes of GAD recruited different pathways, suggesting that comorbid depression in GAD patients would change their neural plasticity.

Dancing with the Sniper: Rasha Abbas and the “Art of Survival” as an Aesthetic Strategy

In the last few decades, a growing dissatisfaction with traditional approaches can be observed in migration and refugee studies. In particular, the widespread focus on the “refugee” and “migrant” as exclusive objects of study has been criticized for its underlying tendency of repeating the binary polarization between migrant and non-migrant, native and foreign as well as majority and minority. This chapter considers the short stories of Syrian journalist and writer Rasha Abbas against this background. Instead of reducing her stories to the depiction of flight and exile, this chapter explores her stories as aesthetic expressions of what can be called the “art of survival”—the concept focusing on strategies of empowerment and tactics to regain autonomy. In Abbas’ prose, this “art of survival” is achieved and expressed through the blending of times and spaces as well as the aesthetic transformation of reality into surreal realms. Experiences of war, displacement, exile, and patterns of exclusion in the new homeland merge into complex pictures of the human capacity to reframe and reinvent a given reality. When viewed from this perspective, the surreal and psychedelic nature of her writing intensifies the power of aesthetic freedom, thus helping overcome traditional representations of migrants and refugees in cultural expressions and literature.

Walkability and accessibility around the Unified Educational Centers of São Paulo

The objective of this article is to draw a brief analysis of the walkability and accessibility of the immediate surroundings of some Unified Educational Centers (CEUs) in São Paulo, through the available information on Geosampa and Google Maps websites, related to enrollments in the municipal network in São Paulo. When evaluating the walkability and accessibility in the immediate surroundings of some CEUs in São Paulo, the contrast between the implantation so generous and inviting for the environments inside the CEU and the maintenance of the existing pattern of exclusion of space for the pedestrian’s circulation in its immediate surroundings becomes clear, leading to an invitation to reflect about how we can try to improve walkability in terms of accessibility and safety.

The Ornamented Shell of a New Bothremydid Turtle from the Uppermost Cretaceous of Niger

A new pleurodiran turtle is described here. It is identified as attributable to Bothremydidae. The new taxon comes from an upper Maastrichtian (Upper Cretaceous) outcrop located in Southwestern Niger (in the Indamane Mount area, belonging to the Abalak Department of the Tahoua Region). Abalakemys chapmanae gen. et sp. nov. is identified by an almost complete large shell of about 65 cm in length. The new bothremydid turtle is recognized as a member of Bothremydodda, showing several autapomorphies (an exclusive ornamental pattern on the plate’s outer surface, covered by small depressions; small fourth pleural scutes, only anteromedially reaching the sixth pair of costal plates; and noticeably wedged posterior plastral lobe toward the posterior region), as well as a unique combination of characters for this clade. This turtle could belong to Nigeremydini, a poorly understood Maastrichtian to Paleocene lineage of Bothremydodda, which integrates large coastal taxa that inhabited the African Trans-Saharan seaway, and for which shell information is currently extremely limited.

Abstract P2-26-06: Association between CK+/CD45+ circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) alterations in advanced breast cancer patients

Abstract Background: Circulating tumor cells (CTCs) in breast cancer (BC) are commonly defined as epithelial cells (EPCAM and cytokeratin (CK) positive), lacking the universal blood cell marker CD45. Nonetheless, CTCs expressing both CK and CD45 (= dual-positive, DP cells) can be observed in the blood of cancer patients. Early evidence suggests that DP cells might derive from the fusion of tumor cells and macrophages, and we have previously demonstrated that they present aberrant genomes and are associated with worse prognosis in BC [1,2]. Here, to further investigate the mechanisms/pathways underlying their presence, we analyzed the association between DP cells and circulating tumor DNA (ctDNA) alterations. Methods: Blood samples were collected from patients with advanced BC (aBC), before starting a new line of therapy. All patients were enrolled in a prospective clinical trial. For CTC and DP cells analysis, 7.5 ml of blood collected in CellSave® tubes was processed with the FDA-approved CellSearch® platform (positivity cutoffs were ≥1 cell for DPcells and ≥5 cells for CTCs). For ctDNA analysis, plasma was collected from Streck stabilizing tubes and analyzed with the Guardant360™ NGS platform for the detection of somatic single nucleotide variants (SNVs), insertions/deletions (indels), gene fusions/rearrangements and copy number variations (CNVs), which were then classified into pathways based on previously defined profiles generated on the Cancer Genome Atlas database (RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Associations between ctDNA-detected gene alterations and circulating cell types were analyzed through chi square test, while mutant allele frequency (MAF) and number of detected alterations (NDA) were tested by Mann Whitney test. Results: We analyzed blood samples from 169 patients with luminal-like (n=80), HER2+ (n=34) and triple-negative (n=52) aBC. DPcells were detected in 85 patients (50.3 %, range 0-53), of which 40 (47 %) were CTC-positive and 45 (53%) CTC-negative. Somatic ctDNA alterations were detected in all analyzed samples. In the overall population, the presence of ≥1 DPcell was associated with SNVs in the cell cycle pathway (p = 0.043), a numerically higher incidence was also observed for CNVs in this pathway. SNVs and CNVs in the cell cycle pathway were associated with CTCs ≥ 5 as well (p = 0.005 and p = 0.003, respectively). Moreover, associations with CTCs ≥ 5 were observed for RTK SNVs and CNVs (p = 0.041 and p = 0.046, respectively), PI3K SNVs and CNVs (p = 0.006 and p = 0.007, respectively), MYC SNVs and CNVs (p = 0.042). No associations were observed in terms of MAF and NDA. In the luminal-like subgroup an association was highlighted for CNVs in the cell cycle pathway, p = 0.038. CTCs ≥ 5 were associated with PI3K SNVs (p = 0.031). In the triple-negative subgroup DPcells were associated with SNVs in the RAF pathway (p = 0.041), whereas CTCs ≥ 5 were associated with PI3K SNVs and CNVs (p = 0.044 and p = 0.024, respectively) and RTK SNVs (p = 0.008). In the HER2 positive subgroup, a higher MAF and number of detected SNVs was observed for samples with ≥1 DPcell (p = 0.0286 and p = 0.0099, respectively). Conclusions: The study analyzed ctDNA features associated with canonical and CK+/CD45+ CTCs, showing differential gene alteration profiles. Cell cycle pathway SNVs were common in both CTC populations, while other pathways (RTK, PI3K, MYC and RAF) were significantly altered in a mutually exclusive pattern. These results suggest that DPcells might have a different biological meaning compared to canonical CTCs. More studies need to be conducted to better characterize this understudied CTC subpopulation and understand their specific contribution to cancer progression.

An extreme environment drives local adaptation ofGenista tinctoria(Fabaceae) from the Mefite (Ansanto Valley, southern Italy)

AbstractThe Mefite in the Ansanto Valley is one of the largest and oldest cold natural carbon dioxide springs (CNCDS) known in the world. This site is characterized by toxic concentrations of CO2 and other harmful gases, and few plant species can survive in this environment. Among these plants, there is an aberrant Genista tinctoria population previously described as G. anxantica. This study aims to advance understanding of evolution over small geographical scales in an extreme environment using G. tinctoria populations from low and high CO2 environments. To investigate differentiation of the Mefite population, we analysed plastid sequences and microsatellite data for populations in the surrounding area. Considering the genetic results, it is evident that the population of the Mefite has an exclusive genetic pattern from both plastid and nuclear points of view with the presence of significant genetic barriers for both genomes analysed, which would point to the isolation of this population from neighbouring G. tinctoria populations. The population of G. tinctoria from the Mefite shows evidence of genetic differentiation from the nearby populations and the genetic indices show discrete variation. Recruitment was confirmed in the Mefite population, an indication that fitness is maintained despite the extreme local conditions. Our results indicate that the potent selection pressure imposed by the Mefite atmosphere has driven genetic differentiation of the local population from nearby G. tinctoria populations. A correct taxonomic rank evaluation and some conservation remarks are also proposed. Our study demonstrates that CO2 concentrations can influence population differentiation and adaptation in plants in a similar way to atmospheric sulphur, herbicides or edaphic conditions.

Identifying rental discrimination on the Flemish housing market: an intersectional approach

ABSTRACT This study aims to identify rental discrimination on the Flemish rental housing market in Belgium, taking the intersectional nature of discrimination into account. Most discrimination studies focus on unequal access based on one individual discrimination ground. This practice eludes the context of the other discrimination grounds in which rental discrimination occurs and neglects the intersectional nature of discrimination. We therefore conducted 8.245 correspondence tests in almost all municipalities in Flanders, the Dutch-speaking part of Belgium. We apply an intersectional lens, by considering the relation and interaction between gender (male/female), ethnic origin (Moroccan/Polish) and the homogeneity of names (homogenous/mixed). We find four strata of rental discrimination, in which Moroccan female rental candidates with a homogenous name experience most discrimination, indicating that multiple categorical identities enforce each other. Without a full intersectional approach, these layered patterns of exclusion would have been hidden behind the bold boundaries of ethnic or gender categorizations.

Is Virtual Cognitive Stimulation Therapy the Future for People with Dementia? An Audit of UK NHS Memory Clinics During the COVID-19 Pandemic

Access to psychosocial interventions for people with dementia, such as Cognitive Stimulation Therapy (CST), has been restricted during the COVID-19 pandemic. Some services have shifted to provision via videoconferencing, but the prevalence of this is unknown. This audit aimed to understand provision of virtual CST (vCST) within National Health Service (NHS) memory clinics throughout the UK and Channel Islands and investigate plans for ongoing CST provision. A cross-sectional survey was circulated to NHS memory clinics, which included closed and open-ended questions to generate quantitative and qualitative data. Thirty-three memory clinics responded to the survey. During the pandemic, 55% of respondents offered vCST, whereas 45% offered no CST. Of those offering vCST, 80% plan to continue with a hybrid model of separate face-to-face and vCST groups, whilst 20% intend to deliver face-to-face CST only. Reported positive aspects of vCST were participant and staff enjoyment, perceived improved digital confidence in participants, and improved accessibility for those who cannot attend face-to-face groups. Negative aspects related to digital poverty, limited digital literacy, support needed from carers, the impact of sensory impairment on engagement, and staff time commitment. Virtual CST has been a feasible alternative to face-to-face services during the pandemic but should not completely replace in-person groups. A hybrid approach would increase accessibility for all. Future research should explore efficacy of vCST and seek to understand patterns of exclusion from such digital interventions.

Dissecting the molecular signatures underlying hybrid oncocytic tumors in Birt-Hogg-Dubé syndrome.

707 Background: Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of renal tumors including the hybrid oncocytic tumors (HOT), renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). HOT are known to exhibit morphological features overlapping between RO and CHRCC. The molecular underpinnings of HOT and the corresponding morphologic correlates remain poorly understood. Herein we aimed to understand the distinct molecular features underlying HOT and how the genomic phenotype differs from CHRCC. Methods: We performed next generation sequencing and single cell sequencing analysis to understand the clinico-pathologic aspects and tumor biology of HOT and CHRCC, including tumor development. This was followed by spatial transcriptome analysis of the distinct HOT tumor compartments, using nanoString GeoMX digital spatial profiler. The candidate biomarker expression was confirmed by immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH), a unique gene expression visualization molecular technology. Results: We discovered unique gene expression signatures underlying the two distinct morphological patterns seen in HOT. FOXI1 and L1CAM show a striking mutually exclusive expression pattern in the two cellular populations seen within this tumor. The signature genes of RO like cells seen within HOT resembles the principal cells of the distal nephron seen in normal kidney; and the signature genes of the CHRCC like cells resembles the intercalated cells of the distal nephron. This suggests distal nephron as the cellular site of origin for HOT. We also nominated tumor specific biomarkers for HOT. Conclusions: We identified unique gene expression signatures which are definitional for HOT and nominated candidate diagnostic biomarkers to help distinguish HOT from other renal tumor subtypes with overlapping morphology. This finding would improve the diagnostic accuracy, assist familial genetic monitoring, and facilitate disease management.

Beyond a seat at the table: imagining educational equity through critical inclusion

ABSTRACT Interlocking mechanisms of exclusion function as gatekeepers to high-quality learning in schools, which perpetuate oppressive conceptions of ability, learning, and intelligence. Across educational ecosystems, these intersecting forms of oppression—including but not limited to racism, ableism, and colonialism—are reified through exclusionary practices that hoard learning opportunities. In this paper, we contend that learning-access disparities are at the crux of educational inequalities, and that theoretical fragmentation across educational disciplines has limited our understanding of entrenched patterns of exclusion and potential solutions. This fragmentation has led to siloed equity conversations and solutions; therefore, we articulate a conceptual framework for inclusive education: Critical Inclusion (InCrit). In doing so, we first engage in a critical-historical review of educational inclusion, including how it has been theorised and operationalised in both research and praxis. We next describe the cross-pollination of the foundational theories on which the conceptual framework stands to emphasise intersectionality and emancipatory education in relation to the vast scholarship on critical inclusion. We then present the framework’s core components, which represent connectors between theory and practice, and illustrative examples. We conclude with a discussion of the cross-systems change required to make meaningful progress toward emancipatory education for all students and achieve critical inclusion in practice.

Transforming a child's claim for loss of earning capacity

This article explores the possible constitutional transformation of a child's delictual claim for loss of earning capacity. As such, it is located at the intersection of the law of delict and child law. The current law on a child's claim for loss of earning capacity is explained first. It is shown that such a claim involves a concurrent violation of the constitutional rights to bodily integrity and property which common-law thinkers call a person's "personal immaterial property". A claim for loss of future earning capacity may be brought by or on behalf of a child in terms of the common law's rules for Aquilian liability. In this regard, it is noted that the assessment of future losses is a controversial legal issue because it necessarily involves speculation about future hypotheticals. While controversial, claims of this nature may be reasonably determined with reference to available evidence. In terms of the law, as it stands, factors that courts consider in quantifying a child's damages for loss of earning capacity include the average probable income, the child's schooling and familial context, wage statistics, and broad judicial discretion. It will be shown that these factors could be applied (and sometimes have been applied) in ways that perpetuate past patterns of exclusion and poverty that are often racially determined - ultimately resulting in some children's claims for loss of earning capacity being pitched below a liveable wage. Relying on the constitutional right to equality and the constitutional best interests of the child standard, it is argued that the common law ought to be developed in this regard to move our law of delict in the direction of distributive justice. In this regard, reference to "liveable wages" and "fairness" (as a consideration in exercising judicial discretion) may be appropriate guidelines used to quantify children's claims for loss of earning capacity in future.

Breakfast Dietary Patterns among Mexican Children Are Related to Total-Day Diet Quality

Background: Mexico has experienced shifts in food availability and consumption patterns over the past few decades from traditional diets to those containing more high-energy density foods, resulting in the development of unhealthful dietary patterns among children and adults. However, to our knowledge it is not known whether breakfast consumption patterns contribute to the overall daily diet of Mexican children.Objective: We examined total-day diet among breakfast consumers compared with breakfast skippers, identified and investigated breakfast dietary patterns in relation to energy and nutrient intakes at breakfast and across the day, and examined these patterns in relation to sociodemographic characteristics.Methods: With the use of nationally representative dietary data (one 24-h recall) from the 2012 Mexican National Health and Nutrition Survey, 3760 children aged 4-13 y were categorized into mutually exclusive breakfast patterns with the use of cluster analysis. The association between breakfast patterns and breakfast skippers with dietary intake at breakfast and for the total day was investigated with the use of multivariate linear regression.Results: Most children (83%) consumed breakfast. Six breakfast dietary patterns were identified (milk and sweetened breads, tortillas and beans, sweetened beverages, sandwiches and quesadillas, eggs, and cereal and milk) and reflected both traditional and more Westernized dietary patterns. Sugar-sweetened beverages were consumed across all patterns. Compared with all breakfast dietary patterns, breakfast skippers had the lowest intake of several nutrients of public health concern. Nutrients to limit that were high at breakfast tended to be high for the total day and vice versa for nutrients to encourage.Conclusions: There was not a single pattern that complied perfectly with the Mexican School Breakfast Guidelines, but changes such as increasing dietary fiber by encouraging more whole grains, fruits, vegetables, and beans and reducing sodium and sugar-sweetened beverages could support compliance with these targets and improve overall diet quality.

Differences in genomic profiles of gastric adenocarcinoma in the US and Japan.

299 Background: Although epidemiological and clinical differences in gastric cancer (GC) between the US and Japan have been reported, genetic differences have not been clarified. We aimed to characterize molecular differences in GC between the two countries. Methods: We collected data between January 2010 and December 2019 from a prospectively maintained database of GC at our US and Japanese centers. After matching clinicopathological backgrounds, including age, sex, clinical T and N status, and tumor location, the genomic profiles of the primary site were compared for 58 patients in each group undergoing surgical resection and had MSK-IMPACT (MSK-Integrated Mutation Profiling of Actionable Cancer Targets), a tumor-normal next generation sequencing assay that can detect alterations in exons and select introns of 505 genes. The MSI sensor algorithm was used to assess microsatellite instability. Genomic alterations were filtered for driver variants using OncoKB, and genes were consolidated into pathways using curated pathway templates from the Cancer Genome Atlas. Results: The clinicopathological characteristics were well matched between 58 patients in each cohort. In the entire cohort, the most commonly altered genes were: TP53 (45%), ARID1A (24%), and ERBB2 (17%) in the US cohort, and TP53 (50%), ARID1A (19%), and ERBB2 (17%) in the Japanese cohort. Although KMT2D was more frequently altered in the US cohort (19% vs. 2%), the two cohorts had no significant differences in other altered genes and gene pathways. The tumor with MSI high was found more frequently in the US cohort (22.4% vs. 5.2%, p = 0.01). Among the MSI-normal tumors, the tumor mutational burden (US: 3.5 muts/Mb and Japanese: 4.1 muts/Mb) and the fraction genome altered (US: 0.37 and Japanese: 0.28) did not significantly differ between the two groups. Additionally, no genes or pathways were significantly enriched in either group. Patterns of mutual exclusivity and co-occurrence amongst genes and pathways were also similar between the two groups. Conclusions: In this original genomic comparison of US and Japanese gastric cancers, matching clinicopathological backgrounds, Japanese and US gastric cancers are remarkably similar at the genomic level, with the possible exception of MSI-high tumor that appear to be more frequent in the US.