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1.
Cell ; 162(3): 648-61, 2015 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-26232230

RESUMEN

We describe automated technologies to probe the structure of neural tissue at nanometer resolution and use them to generate a saturated reconstruction of a sub-volume of mouse neocortex in which all cellular objects (axons, dendrites, and glia) and many sub-cellular components (synapses, synaptic vesicles, spines, spine apparati, postsynaptic densities, and mitochondria) are rendered and itemized in a database. We explore these data to study physical properties of brain tissue. For example, by tracing the trajectories of all excitatory axons and noting their juxtapositions, both synaptic and non-synaptic, with every dendritic spine we refute the idea that physical proximity is sufficient to predict synaptic connectivity (the so-called Peters' rule). This online minable database provides general access to the intrinsic complexity of the neocortex and enables further data-driven inquiries.


Asunto(s)
Microscopía Electrónica de Rastreo/métodos , Microtomía/métodos , Neocórtex/ultraestructura , Neuronas/ultraestructura , Animales , Automatización , Axones/ultraestructura , Dendritas/ultraestructura , Ratones , Neocórtex/citología , Sinapsis/ultraestructura , Vesículas Sinápticas/ultraestructura
2.
J Natl Compr Canc Netw ; 22(3): 158-166, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38626807

RESUMEN

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/epidemiología , Detección Precoz del Cáncer/métodos , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Imagen por Resonancia Magnética
3.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-33649197

RESUMEN

Epithelia have distinct cellular architectures which are established in development, reestablished after wounding, and maintained during tissue homeostasis despite cell turnover and mechanical perturbations. In turn, cell shape also controls tissue function as a regulator of cell differentiation, proliferation, and motility. Here, we investigate cell shape changes in a model epithelial monolayer. After the onset of confluence, cells continue to proliferate and change shape over time, eventually leading to a final architecture characterized by arrested motion and more regular cell shapes. Such monolayer remodeling is robust, with qualitatively similar evolution in cell shape and dynamics observed across disparate perturbations. Here, we quantify differences in monolayer remodeling guided by the active vertex model to identify underlying order parameters controlling epithelial architecture. When monolayers are formed atop an extracellular matrix with varied stiffness, we find the cell density at which motion arrests varies significantly, but the cell shape remains constant, consistent with the onset of tissue rigidity. In contrast, pharmacological perturbations can significantly alter the cell shape at which tissue dynamics are arrested, consistent with varied amounts of active stress within the tissue. Across all experimental conditions, the final cell shape is well correlated to the cell proliferation rate, and cell cycle inhibition immediately arrests cell motility. Finally, we demonstrate cell cycle variation in junctional tension as a source of active stress within the monolayer. Thus, the architecture and mechanics of epithelial tissue can arise from an interplay between cell mechanics and stresses arising from cell cycle dynamics.


Asunto(s)
Ciclo Celular , Forma de la Célula , Células Epiteliales/metabolismo , Matriz Extracelular/metabolismo , Estrés Fisiológico , Animales , Perros , Células Epiteliales/citología , Células de Riñón Canino Madin Darby
4.
Gastroenterology ; 163(2): 437-448.e1, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35483444

RESUMEN

BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.


Asunto(s)
Neoplasias del Colon , Neoplasias Gastrointestinales , Detección Precoz del Cáncer , Humanos , Modelos Lineales , Población Rural , Estados Unidos/epidemiología
5.
Gastrointest Endosc ; 97(1): 2-10.e1, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36084717

RESUMEN

BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility. METHODS: Databases were queried through December 2021 to identify studies that examined upper endoscopy screening in LS using EGD. Mantel-Haenszel pooled odds ratios and 95% confidence intervals (CIs) for outcomes were constructed using a random-effects model to identify pooled odds of endoscopic findings in persons with LS. Event rates for detection of gastric and duodenal cancers, high-risk lesions, and clinically actionable findings were calculated. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Nine studies were identified with 2356 LS patients undergoing approximately 7838 EGDs. In total, 47 LS-associated UGI cancers (18 gastric and 29 duodenal cancers), 237 high-risk lesions, and 335 clinically actionable findings were identified. The pooled event rate for detection of any UGI cancer, high-risk lesions, and clinically actionable findings during screening were .9% (95% CI, .3-2.1; I2 = 89%), 4.2% (95% CI, 1.6-10.9; I2 = 98%), and 6.2% (95% CI, 2.2-16.5; I2 = 99%), respectively. There was no difference between LS-associated gene and gastric or duodenal cancer detection. CONCLUSIONS: In LS, there is evidence that endoscopic screening detects UGI cancers, precancerous lesions, and other clinically actionable findings that favor its use as a part of cancer risk management in LS.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Duodenales , Lesiones Precancerosas , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Detección Precoz del Cáncer , Endoscopía Gastrointestinal , Lesiones Precancerosas/diagnóstico
6.
Soft Matter ; 18(11): 2168-2175, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35212696

RESUMEN

In development and homeostasis, multi-cellular systems exhibit spatial and temporal heterogeneity in their biochemical and mechanical properties. Nevertheless, it remains unclear how spatiotemporally heterogeneous forces affect the dynamical and mechanical properties of confluent tissue. To address this question, we study the dynamical behavior of the two-dimensional cellular vertex model for epithelial monolayers in the presence of fluctuating cell-cell interfacial tensions, which is a biologically relevant source of mechanical spatiotemporal heterogeneity. In particular, we investigate the effects of the amplitude and persistence time of fluctuating tension on the tissue dynamics. We unexpectedly find that the long-time diffusion constant describing cell rearrangements depends non-monotonically on the persistence time, while it increases monotonically as the amplitude increases. Our analysis indicates that at low and intermediate persistence times tension fluctuations drive motion of vertices and promote cell rearrangements, while at the highest persistence times the tension in the network evolves so slowly that rearrangements become rare.


Asunto(s)
Modelos Biológicos , Fenómenos Físicos
7.
Dig Dis Sci ; 67(8): 3890-3903, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34554365

RESUMEN

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Adulto , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Hospitalización , Humanos , Terapia de Inmunosupresión , Factores de Riesgo
8.
Clin Gastroenterol Hepatol ; 19(9): 1967-1969, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-31351134

RESUMEN

The incidence of colorectal cancer (CRC) and cancer-related mortality has increased in patients <55 years old.1 Consensus on optimal intervals for post-CRC surveillance colonoscopy in young patients is lacking. The primary endpoint of this study was comparison of rates of metachronous advanced neoplasia (AN) in patients diagnosed with CRC at <50 and 50-75 years. The secondary aim was to evaluate risk factors of metachronous AN.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Primarias Secundarias , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/epidemiología , Factores de Riesgo
9.
BMC Cancer ; 21(1): 966, 2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34454457

RESUMEN

BACKGROUND: Adherence to colorectal cancer screening in the United States is suboptimal, particularly in medically underserved populations due to significant barriers to care. Unique accessible, low-cost, and non-invasive screening tests for this population could greatly benefit current rates. In this article, we assess patient preference and the impact of offering a blood-based test on screening rates in a cost-free health fair setting from April 2017 to April 2019. METHODS: Participants who met colorectal cancer screening eligibility criteria set forth by the United States Preventive Services Task Force were recommended to attend the colon cancer screening station. Those participants who elected to attend were offered various, accepted screening methods, and if they declined, were offered alternative blood-based testing. Screening rates, test outcomes, and the rate of follow up completion of colonoscopy were measured and compared with historic screening outcomes. RESULTS: Of 1401 participants who were recommended to attend, 640 (45.7%) participants were evaluated at the colon cancer screening station, of whom 460 were eligible for testing. Amongst these, none selected colonoscopy, 30 (6.5%) selected fecal immunochemical testing, and 430 (93.5%) selected blood-based testing. Only 2 participants returned the fecal immunochemical tests. In the blood test cohort, 88 were positive and 20 received a follow up colonoscopy. CONCLUSIONS: Based on this assessment, blood-based testing is an effective method to increase screening rates in medically underserved populations, though efforts to further improve access to follow up colonoscopy are necessary.


Asunto(s)
Neoplasias del Colon/diagnóstico , Detección Precoz del Cáncer/métodos , Pruebas Hematológicas/métodos , Área sin Atención Médica , Cooperación del Paciente/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/sangre , Neoplasias del Colon/epidemiología , Colonoscopía , Femenino , Florida/epidemiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Sangre Oculta , Cooperación del Paciente/psicología , Pronóstico , Estudios Retrospectivos
10.
Soft Matter ; 17(45): 10242-10253, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33463648

RESUMEN

Machine learning techniques have been used to quantify the relationship between local structural features and variations in local dynamical activity in disordered glass-forming materials. To date these methods have been applied to an array of standard (Arrhenius and super-Arrhenius) glass formers, where work on "soft spots" indicates a connection between the linear vibrational response of a configuration and the energy barriers to non-linear deformations. Here we study the Voronoi model, which takes its inspiration from dense epithelial monolayers and which displays anomalous, sub-Arrhenius scaling of its dynamical relaxation time with decreasing temperature. Despite these differences, we find that the likelihood of rearrangements can nevertheless vary by several orders of magnitude within the model tissue and extract a local structural quantity, "softness," that accurately predicts the temperature dependence of the relaxation time. We use an information-theoretic measure to quantify the extent to which softness determines impending topological rearrangements; we find that softness captures nearly all of the information about rearrangements that is obtainable from structure, and that this information is large in the solid phase of the model and decreases rapidly as state variables are varied into the fluid phase.


Asunto(s)
Vidrio , Temperatura
11.
Gastroenterol Nurs ; 44(4): 240-251, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34149038

RESUMEN

COVID-19 was declared a pandemic in March 2020 by the World Health Organization. To minimize exposure and because of limited personal protective equipment resources, most gastroenterology practices were curtailed/modified during the surge, with slow reopening to a normal/semi-normal schedule. Gastroenterology healthcare workers have been impacted greatly by COVID-19, resulting in job and wage insecurity. The aim of our study was to understand the impact of COVID-19 on gastroenterology healthcare workers across the United States. A web-based survey, consisting of 40 questions, was disseminated among gastroenterology practices across the United States via en masse e-mails and direct contact by authors. In total, 223 gastroenterology healthcare workers completed the survey; 56.1% were from academic settings. COVID-19 impacted the work schedule of 85.2% of participants, with reduced weekly work hours (38.1%), duty reassignment (22.4%), and furlough (13.9%). Uncertainty about job and/or future wages/benefits after reopening was noted in 41%, which was significantly associated with the presence of physical (p = .021) and mental/emotional symptoms (p = .045). Worsening of pre-existing physical and/or mental/emotional conditions was observed in 53%. Inadequate personal protective equipment availability, lack of temporary housing and/or childcare facilities, as well as job insecurity appear to be the important factors leading to worsening physical/mental/emotional conditions among gastroenterology healthcare workers.


Asunto(s)
COVID-19 , Gastroenterología , Personal de Salud , Salud Mental , Personal de Salud/psicología , Humanos , Pandemias , SARS-CoV-2 , Estados Unidos/epidemiología , Carga de Trabajo
12.
Cancer Causes Control ; 31(9): 815-826, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32462560

RESUMEN

PURPOSE: The prognosis for gastric carcinoma (GC) remains challenging with less than 35% of patients surviving 5 years. GC survival varies greatly by anatomical site, cardia and non-cardia. However, these important differences have not been thoroughly studied in relation to the increasing diversity in US populations such as Florida. In this study we examined, for the first time, the effect of race-ethnicity on risk of death from GC controlling for potential risk factors separately for cardia and non-cardia GCs. METHODS: Data on GCs diagnosed in Florida from 2005-2016 were obtained from the statewide cancer registry. Age-standardized GC-specific 5-year survival was computed by anatomical site and race-ethnicity. In addition, a competing risk analysis was performed to assess prognostic factors and to estimate subdistribution hazard ratios of death from GC. RESULTS: Whites had high proportions of cardia GC (43.9%) compared to all racial/ethnic minorities (10.9%, 19.6%, and 13.8% in Blacks, Hispanics, and Asians, respectively; p < .0001). Among 12,302 cases included, there were 7534 deaths from GC and 1179 from other causes. Age standardized GC-specific 5-year survival was significantly lower for Whites (28.0%) compared to Blacks (31.6%), Hispanics (37.6%), and Asians, (39.6%) and significantly lower for cardia GC (25.0%, 95% CI 23.4-26.6) compared to non-cardia GC (37.0%, 95% CI 35.5-38.4). Multivariable competing risk analysis in patients with non-cardia GC showed that Asians (sHR: 0.64, 95% CI 0.51-0.80), Hispanics (sHR 0.71, 95% CI 0.64-0.78), and Blacks (sHR 0.83, 95% CI 0.75-0.92) all had lower risks of death from GC compared to Whites. In patients with cardia GC, only Hispanics had statistically significant lower risk of death from GC than Whites (sHR 0.84, 95% CI 0.74-0.95, p = 0.005). CONCLUSIONS: The study of racial/ethnic survival disparities in patients with GC in Florida reveals Whites as the most disadvantaged group. Whites are more afflicted by cardia GC, which is associated with higher risk of death than non-cardia GC. However, even within non-cardia GC, Whites had higher risk of death than the other racial-ethnic groups. Commonly assessed survival determinants do not adequately explain these unusual disparities; thus, further investigation is warranted.


Asunto(s)
Hispánicos o Latinos/estadística & datos numéricos , Neoplasias Gástricas/etnología , Neoplasias Gástricas/mortalidad , Adolescente , Adulto , Anciano , Pueblo Asiatico/estadística & datos numéricos , Población Negra/estadística & datos numéricos , Femenino , Florida/epidemiología , Disparidades en el Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de Riesgo , Población Blanca/estadística & datos numéricos , Adulto Joven
13.
Soft Matter ; 16(13): 3325-3337, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32196025

RESUMEN

Surface tension governed by differential adhesion can drive fluid particle mixtures to sort into separate regions, i.e., demix. Does the same phenomenon occur in confluent biological tissues? We begin to answer this question for epithelial monolayers with a combination of theory via a vertex model and experiments on keratinocyte monolayers. Vertex models are distinct from particle models in that the interactions between the cells are shape-based, as opposed to distance-dependent. We investigate whether a disparity in cell shape or size alone is sufficient to drive demixing in bidisperse vertex model fluid mixtures. Surprisingly, we observe that both types of bidisperse systems robustly mix on large lengthscales. On the other hand, shape disparity generates slight demixing over a few cell diameters, a phenomenon we term micro-demixing. This result can be understood by examining the differential energy barriers for neighbor exchanges (T1 transitions). Experiments with mixtures of wild-type and E-cadherin-deficient keratinocytes on a substrate are consistent with the predicted phenomenon of micro-demixing, which biology may exploit to create subtle patterning. The robustness of mixing at large scales, however, suggests that despite some differences in cell shape and size, progenitor cells can readily mix throughout a developing tissue until acquiring means of recognizing cells of different types.


Asunto(s)
Cadherinas/genética , Adhesión Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Cadherinas/química , Forma de la Célula/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Humanos , Propiedades de Superficie
14.
Proc Natl Acad Sci U S A ; 114(40): 10601-10605, 2017 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-28928147

RESUMEN

Nanometrically thin glassy films depart strikingly from the behavior of their bulk counterparts. We investigate whether the dynamical differences between a bulk and thin film polymeric glass former can be understood by differences in local microscopic structure. Machine learning methods have shown that local structure can serve as the foundation for successful, predictive models of particle rearrangement dynamics in bulk systems. By contrast, in thin glassy films, we find that particles at the center of the film and those near the surface are structurally indistinguishable despite exhibiting very different dynamics. Next, we show that structure-independent processes, already present in bulk systems and demonstrably different from simple facilitated dynamics, are crucial for understanding glassy dynamics in thin films. Our analysis suggests a picture of glassy dynamics in which two dynamical processes coexist, with relative strengths that depend on the distance from an interface. One of these processes depends on local structure and is unchanged throughout most of the film, while the other is purely Arrhenius, does not depend on local structure, and is strongly enhanced near the free surface of a film.

15.
Soft Matter ; 15(44): 9133-9149, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31674622

RESUMEN

Recent work on particle-based models of tissues has suggested that any finite rate of cell division and cell death is sufficient to fluidize an epithelial tissue. At the same time, experimental evidence has indicated the existence of glassy dynamics in some epithelial layers despite continued cell cycling. To address this discrepancy, we quantify the role of cell birth and death on glassy states in confluent tissues using simulations of an active vertex model that includes cell motility, cell division, and cell death. Our simulation data is consistent with a simple ansatz in which the rate of cell-life cycling and the rate of relaxation of the tissue in the absence of cell cycling contribute independently and additively to the overall rate of cell motion. Specifically, we find that a glass-like regime with caging behavior indicated by subdiffusive cell displacements can be achieved in systems with sufficiently low rates of cell cycling.


Asunto(s)
Simulación por Computador , Células Epiteliales/citología , Epitelio/química , Modelos Biológicos , Apoptosis , Fenómenos Biomecánicos , Movimiento Celular , Células Epiteliales/química , Células Epiteliales/fisiología , Cinética , Mitosis , Transición de Fase
16.
Clin Gastroenterol Hepatol ; 16(12): 1911-1918.e2, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30130624

RESUMEN

BACKGROUND & AIMS: Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome. METHODS: We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses. RESULTS: Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P = .02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P < .01). On multivariate analysis, African American race, older age, and medical center were independently associated with lack of referral for genetic evaluation and genetic testing. CONCLUSION: In a retrospective analysis, we found that despite similar rates of colorectal tumor analysis, minority patients are less likely to be recommended for genetic evaluation or to undergo germline testing for Lynch syndrome. Improvements in institutional practices in follow up after tumor testing could reduce barriers to diagnosis of Lynch diagnosis in minorities.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/estadística & datos numéricos , Pruebas Genéticas/estadística & datos numéricos , Síndromes Neoplásicos Hereditarios/diagnóstico , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Anciano , Etnicidad , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Grupos Raciales , Estudios Retrospectivos
17.
Phys Rev Lett ; 120(5): 058001, 2018 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-29481188

RESUMEN

How can dense biological tissue maintain sharp boundaries between coexisting cell populations? We explore this question within a simple vertex model for cells, focusing on the role of topology and tissue surface tension. We show that the ability of cells to independently regulate adhesivity and tension, together with neighbor-based interaction rules, lets them support strikingly unusual interfaces. In particular, we show that mechanical- and fluctuation-based measurements of the effective surface tension of a cellular aggregate yield different results, leading to mechanically soft interfaces that are nevertheless extremely sharp.


Asunto(s)
Comunicación Celular/fisiología , Modelos Biológicos , Agregación Celular/fisiología , Fenómenos Fisiológicos Celulares , Simulación por Computador , Tensión Superficial
18.
Soft Matter ; 14(17): 3397-3403, 2018 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-29667689

RESUMEN

Vertex models are a popular approach to simulating the mechanical and dynamical properties of dense biological tissues, describing the tissue as a network of polygons. Recently a class of two-dimensional vertex models was shown to exhibit a disordered rigidity transition controlled by the preferred cellular geometry, which was subsequently echoed by experimental findings. An attractive variant of these models uses a Voronoi tessellation to describe the cells, which reduces the number of degrees of freedom as compared the original vertex model. The Voronoi model was also endowed with a non-equilibrium model of cellular motility, leading to rich, glassy behavior. This glassy behavior was suggested to be inextricably linked to an underlying jamming transition. We test this conjecture, exploring the low-effective-temperature limit of the 2D Voronoi model by studying cell trajectories from detailed dynamical simulations in combination with rigidity measurements of energy-minimized disordered cell configurations. We find that the zero-temperature limit of this model has no unjamming transition. We show that this absence of an unjamming transition is intimately linked to the marginality of the model, i.e. the fact that the constraints imposed on cell areas and perimeters precisely balance the number of degrees of freedom in the model. Our work suggests that constraint counting arguments are useful to understand rigidity in a broad class of models of dense biological tissues.


Asunto(s)
Modelos Biológicos , Movimiento Celular
19.
Soft Matter ; 14(36): 7435-7445, 2018 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-30152493

RESUMEN

Purely repulsive active particles spontaneously undergo motility-induced phase separation (MIPS) into condensed and dilute phases. Remarkably, the mechanical tension measured along the interface between these phases is negative. In equilibrium this would imply an unstable interface that wants to expand, but these out-of-equilibrium systems display long-time stability and have intrinsically stiff boundaries. Here, we study this phenomenon in detail using active Brownian particle simulations and a novel frame of reference. By shifting from the global (or laboratory) frame to a local frame that follows the dynamics of the phase boundary, we observe correlations between the local curvature of the interface and the measured value of the tension. Importantly, our analysis reveals that curvature drives sustained local tangential motion of particles within a surface layer in both the gas and the dense regions. The combined tangential current in the gas and local "self-shearing" of the surface of the dense phase suggest a stiffening interface that redirects particles along itself to heal local fluctuations. These currents restore the otherwise wildly fluctuating interface through an out-of-equilibrium Marangoni effect. We discuss the implications of our observations on phenomenological models of interfacial dynamics.

20.
J Clin Gastroenterol ; 52(9): 817-820, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29095418

RESUMEN

BACKGROUND: Non-Hispanic blacks (NHB) and Hispanics often present with advanced colorectal cancer (CRC). The aim of the study was to characterize CRC differences among Hispanics, NHB, and non-Hispanic whites (NHW). METHODS: A cross-sectional analysis and logistic regression of 2009 Florida Agency for Healthcare Administration Hospital Admission Database data for CRC using the International Classification of Diseases, 9th Revision, Clinical Modification codes was performed. Outcomes included CRC location, frequency of metastasis and colectomy rates. Each minority group was compared with NHW. RESULTS: A total of 34,577 patients were NHW, 5190 were NHB, and 5033 were Hispanic. NHB had more proximal CRC [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.09-1.25; P<0.0001]; Hispanics had more distal CRC (OR, 0.90; 95% CI, 0.83-0.96; P=0.0024). Hispanics had increased metastases (OR, 1.11; 95% CI, 1.02-1.22; P=0.04). NHB and Hispanics underwent fewer colectomies [(OR, 0.93; 95% CI, 0.86-0.99; P=0.03) and (OR, 0.9; 95% CI, 0.84-0.97; P=0.001), respectively]. CONCLUSIONS: Disparities in CRC metastases and colectomy rates exist among these racial groups in Florida. This work should serve as a foundation to study potential causes and to design culture-specific interventions.


Asunto(s)
Colectomía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Disparidades en el Estado de Salud , Disparidades en Atención de Salud/etnología , Negro o Afroamericano/estadística & datos numéricos , Anciano , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/patología , Estudios Transversales , Femenino , Florida , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Población Blanca/estadística & datos numéricos
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