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Adequate lymph node (LN) excision is imperative for pathologic staging and determination of adjuvant treatment. he 2004–2017 National Cancer Database (NCDB) was queried for curative colon cancer resections. Tumors were categorized by location: left, right, and transverse colon cancers. Adequate (12–20 LNs) vs. inadequate (<12 LNs) lymphadenectomy was examined and sub-analysis of <12 LNs, 12–20 LNs or >20 LNs. Primary outcome was predictors of inadequate lymph node retrieval. Of 101,551 patients, 11.2% (11,439) had inadequate lymphadenectomy. The inadequate lymphadenectomy rate steadily decreased. On multivariable analysis, inadequate LN retrieval was associated with transverse (OR 1.49, CI [1.30–1.71]) and left colon cancers (OR 2.66, CI [2.42–2.93], whereas income >$63,333 had decreased likelihood of inadequate LN retrieval (OR 0.68, CI[0.56–0.82]. We are making the grade as NCDB data demonstrates a steady decrease in inadequate lymphadenectomy (2004–2017). There remain socioeconomic risk factors for inadequate lymphadenectomy that need to be addressed. [Display omitted] •Adequate lymphadenectomy for colon cancer resections has steadily increased.•Patients with >20 lymph nodes retrieved had optimal 5 year overall survival.•There are socioeconomic variables that predict inadequate lymph node retrieval.

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 - a component of the transcription elongation complex P-TEFb - bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.

Functional dependence (FD) is associated with poor postoperative outcomes. We investigated the influence of FD on the postoperative outcomes of colectomy. The 2012–2020 National Surgical Quality Improvement Program was queried for patients who had undergone colectomy for diverticulitis. The patients were analyzed based on FD or functionally independent (FI) status. Of the 62,409 patients 991 (1.6%) were FD. Compared to FI patients, those with FD were older (mean age, 72.7 vs. 59.1 years, p < 0.001), with higher comorbidities and more unplanned open procedures (79.7% vs. 38.0%, p < 0.001). After adjusting for American Society of Anesthesia status, age, and comorbidities, the FD patients were 1.12 times (95% CI:1.07–1.17) more likely to have postoperative morbidity and 1.53 times (95% CI: 1.2–1.82) more likely to have 30-day mortality. Dependent functional status is an independent risk factor for complications after surgery for diverticulitis. •Functional dependence (FD) is associated with poor postoperative outcomes.•FD status is an independent risk factor for post-colectomy complications and death.•Patient FD status should be considered when planning colectomy for diverticulitis.

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 - a component of the transcription elongation complex P-TEFb - bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.

High population density should drive individuals to more frequently share space and interact, producing better-connected spatial and social networks [1–4]. Although this theory is fundamental to our understanding of disease dynamics [2,5–8], it remains unconfirmed how local density generally drives individuals’ positions within their networks, which reduces our ability to understand and predict density-dependent processes [4,9,10]. Here we provide the first general evidence that density drives greater network connectedness at fine spatiotemporal scales, at the scale of individuals within wild animal populations. We analysed 36 datasets of simultaneous spatial and social behaviour in >58,000 individual animals, spanning 30 species of fish, reptiles, birds, mammals, and insects. 80% of systems exhibited strong positive relationships between local density and network centrality. However, >80% of relationships were nonlinear and 75% became shallower at higher values, signifying that demographic and behavioural processes counteract density’s effects, thereby producing saturating trends [11–15]. Density’s effect was much stronger and less saturating for spatial than social networks, such that individuals become disproportionately spatially connected rather than socially at higher densities. Consequently, ecological processes that depend on spatial connections (e.g. indirect pathogen transmission, resource competition, and territory formation) are likely more density-dependent than those involving social interactions (e.g. direct pathogen transmission, aggression, and social learning). These findings reveal fundamental ecological rules governing societal structuring, with widespread implications. Identifying scaling rules based on processes that generalise across systems, such as these patterns of density dependence, might provide the ability to predict network structures in novel systems.

Robust methods for characterizing the cellular architecture (cytoarchitecture) of the brain are needed to differentiate brain areas, identify neurological diseases, and model architectural differences across species. Current methods for mapping the cytoarchitecture and, in particular, identifying laminar (layer) divisions in tissue samples require the expertise of trained neuroanatomists to manually annotate the various regions-of-interest and cells within an image. However, as neuroanatomical datasets grow in volume, manual annotations become inefficient, impractical, and risk the potential of biasing results. In this paper, we propose an automated framework for cellular detection and density estimation that enables the detection of laminar divisions within retinal and neocortical histology datasets. Our approach for layer detection uses total variation minimization to find a small number of change points in the density that signify the beginning and end of each layer. We apply these methods to micron-scale histology images from a variety of cortical areas of the mouse brain and retina, as well as synthetic datasets. Our results demonstrate the feasibility of using automation to reveal the cytoarchitecture of neurological samples in high-resolution images.