Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage ...larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.
MESSENGER observations from Mercury orbit reveal that a large contiguous expanse of smooth plains covers much of Mercury's high northern latitudes and occupies more than 6% of the planet's surface ...area. These plains are smooth, embay other landforms, are distinct in color, show several flow features, and partially or completely bury impact craters, the sizes of which indicate plains thicknesses of more than 1 kilometer and multiple phases of emplacement. These characteristics, as well as associated features, interpreted to have formed by thermal erosion, indicate emplacement in a flood-basalt style, consistent with x-ray spectrometric data indicating surface compositions intermediate between those of basalts and komatiites. The plains formed after the Caloris impact basin, confirming that volcanism was a globally extensive process in Mercury's post—heavy bombardment era.
Background
Limited data are available on the development of skin cancer and the associated risk factors for non‐White liver transplant (LT) recipients. The aim of this study is to determine the ...incidence of newly diagnosed skin cancer postoperatively and to identify the risk factors for the development of skin cancer in non‐White LT recipients.
Methods
We conducted an initial retrospective chart review of non‐White LT patients who received a transplant at our center between January 1, 2011, and December 31, 2013.
Results
Of the 96 patients in the study cohort, 32% were Black, 17% were Asian, 15% were White Hispanic, and 10% were Black Hispanic. One patient had a history of nonmelanoma skin cancer before transplant. No skin cancers were diagnosed during follow‐up (median, 1.3 years; range, 17 days to 8.6 years).
Conclusion
Our center’s experience is consistent with the literature and suggests that the incidence of newly diagnosed skin cancer in non‐White liver transplant recipients is low. Longer follow‐up may provide additional insights into the specific risk factors for the posttransplant development of skin cancer.
People with HIV (PHIV) are living longer and experiencing non-AIDS defining cancers (NADC). Epigenetic aging biomarkers have been linked to cancer risk, and cancer is now a leading cause of death in ...PHIV, but these biomarkers have not been investigated in PHIV and cancer.
In order to compare epigenetic age by HIV status, HIV-uninfected participants were matched to PHIV by reported age, tumor site, tumor sequence number, and treatment status.
DNA from blood was assayed using Illumina MethylationEPIC BeadChip and estimated immune cell composition and three epigenetic clocks: Horvath, GrimAge, and epiTOC2. Age acceleration by clock was computed as the residual from the expected value, calculated using linear regression, for each study participant. Comparisons across HIV status used the Wilcoxon rank sum test. Hazard ratios and 95% confidence intervals for the association between age acceleration and survival in PHIV were estimated with Cox regression.
Among 65 NADC participants with HIV and 64 without, biological age from epiTOC2 (p < 0.0001) and GrimAge (p = 0.017) was significantly higher in PHIV. Biological age acceleration was significantly higher in PHIV using epiTOC2 (p < 0.01) and GrimAge (p < 0.0001), with the difference in the GrimAge remaining statistically significant after adjustment for immune cell composition. Among PHIV, GrimAge acceleration was significantly associated with increased risk of death (HR: 1.11; 95% CI:1.04-1.18).
We observed a higher epigenetic age in PHIV with a NADC diagnosis compared to their HIV-uninfected counterparts, as well as a significant association between this accelerated biological aging and survival for patients diagnosed with a NADC.
e13612
Background: Use of electronic Patient Reported Outcomes (ePRO) tools in the routine care of cancer patients remains challenging despite data showing that they can improve resource utilization ...and patient outcomes. Patients with head and neck cancer during intensive therapy with radiation therapy (RT) may particularly benefit from interventions focused on early symptom management. Methods: 34 patients with head and neck cancer were enrolled in an implementation study and received ePROs integrated within the electronic medical record (EMR) weekly during radiation therapy (RT) within a large integrated health care delivery system. ePROs consisted of the FACT G7 and FACT-HN. After completion of each survey on the patient portal, a radiation oncology RN documented any abnormal findings and subsequent interventions using a standardized format within the EMR. If patients did not have access to the patient portal or had language barriers, they could complete ePROs with a translator by phone or video. Results: Between January and December of 2021, 34 patients with head and neck cancer receiving curative RT were enrolled. The median age 65 years (range 46-84). 74% of patients were male. 59% were white, 26% Asian/PI, 5% Black, and 5% Hispanic. The most common primary cancer sites were: oropharynx (32%), nasopharynx (24%), larynx (18%), oral cavity (9%). 65% of patients received concurrent chemotherapy with RT and 35% received RT alone. 97.4% of patients had access to the online portal. The total number of surveys completed was 194 with a median of 7 per patient (range 1-8). There was a total of 887 abnormal findings reported and 887 documented and corresponding interventions resulting in a 100% intervention rate. Over the course of RT the mean number of abnormal findings increased from 2.26 at baseline (n = 34) to 6.27 at week 7 (n = 24), P < 0.0001. Hospitalizations and Emergency Department (ED) visit data were collected during the study and up to 30 days from last day of RT. There was a total of 2 hospitalizations and 8 ED visits. Conclusions: ePROs integrated within the patient portal and EMR are feasible during RT for patients with head and neck cancer within a large integrated health care system. The use of ePROs integrated within the patient portal and EMR can lead to a high rate of intervention. The increasing number of abnormal findings on ePRO during intensive treatment for head and neck cancer is consistent with known patterns of toxicity and confirm the value of studying methods for improving quality of life in this patient population.Table: see text
Abstract
The increased use of next‐generation sequencing has led to the detection of pathogenic
TP53
variants in the germline setting in patients without a personal or family history consistent with ...Li–Fraumeni syndrome (LFS). These variants can represent low‐penetrance LFS, mosaic LFS, or clonal hematopoiesis of indeterminate potential. Additionally,
TP53
variants of uncertain significance can be detected in patients with a history suspicious for LFS. The interpretation of the significance of these variants can be challenging but is crucial for an accurate diagnosis and appropriate medical management. This retrospective case review provides illustrative examples of the interpretation of challenging
TP53
results through multidisciplinary expertise and use of a flowchart. The authors describe eight patients with
TP53
variants associated with ambiguous diagnoses and, for each case, describe how the results were interpreted and the medical care that was implemented. This report presents illustrative cases to help guide clinicians to reach definitive diagnoses for patients when confronted with
TP53
variants that are inconsistent with the clinical picture and to add to the body of literature regarding interpretation and medical management of
TP53
variants discovered on germline testing.
Multiple myeloma (MM) incidence, mortality, and survival varies by race and ethnicity but the causes of these differences remain unclear. We investigated demographic, clinical, and molecular features ...of diverse MM patients to elucidate mechanisms driving clinical disparities. This study included 495 MM patients (self-reported Hispanic, n=45; non-Hispanic Black, n=52; non-Hispanic White, n=398). Hispanic and non-Hispanic Black individuals had an earlier age of onset than non-Hispanic White individuals (53 and 57 versus 63 years, respectively, p<0.001). There were no differences in treatment received by race and ethnicity groups, but non-Hispanic Black patients had a longer time to hematopoietic cell transplant than non-Hispanic White patients (376 days versus 248 days, p=0.01). Overall survival (OS) was improved for non-Hispanic Black compared to non-Hispanic White patients (HR 0.50, 95% CI 0.31-0.81, p=0.005), although this association was attenuated after adjusting for clinical features (HR 0.62, 95% CI 0.37-1.03, p=0.06). Tumor mutations in IRF4 were most common in Hispanic patients, and mutations in SP140, AUTS2, and SETD2 were most common in non-Hispanic Black patients. Differences in tumor expression of BCL7A, SPEF2, and ANKRD26 were observed by race and ethnicity. Clonal hematopoiesis was observed in 12% of patients and associated with inferior OS in non-Hispanic Black patients compared to patients without clonal hematopoiesis (HR 4.36, 95% CI 1.36-14.00), although this association was attenuated after adjusting for prognostic factors. This study provides insight into differences in molecular features that may drive clinical disparities in MM patients receiving comparable treatment, with the novel inclusion of Hispanic individuals.
CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting ...of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 7B9. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNF alpha, TNF beta, and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The human and murine genes map to 9q33 and the proximal region of chromosome 4, respectively.
PDF
