Cis-eQTL-Based Trans-Ethnic Meta-Analysis Reveals Novel Genes Associated with Breast Cancer Risk

Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute\u27s Up for a Challenge (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to examine associations between imputed gene expression and breast cancer risk. In particular, we used reference datasets describing the breast tissue and whole blood transcriptomes to impute expression levels in breast cancer cases and controls. In trans-ethnic meta-analyses of U4C and UK Biobank data, we found significant associations between breast cancer risk and the expression of RCCD1 (joint p-value: 3.6x10-06) and DHODH (p-value: 7.1x10-06) in breast tissue, as well as a suggestive association for ANKLE1 (p-value: 9.3x10-05). Expression of RCCD1 in whole blood was also suggestively associated with disease risk (p-value: 1.2x10-05), as were expression of ACAP1 (p-value: 1.9x10-05) and LRRC25 (p-value: 5.2x10-05). While genome-wide association studies (GWAS) have implicated RCCD1 and ANKLE1 in breast cancer risk, they have not identified the remaining three genes. Among the genetic variants that contributed to the predicted expression of the five genes, we found 23 nominally (p-value \u3c 0.05) associated with breast cancer risk, among which 15 are not in high linkage disequilibrium with risk variants previously identified by GWAS. In summary, we used a transcriptome-based approach to investigate the genetic underpinnings of breast carcinogenesis. This approach provided an avenue for deciphering the functional relevance of genes and genetic variants involved in breast cancer

A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma

Obesity and the microvasculature

Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 μm [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists

Transcriptomic and anatomical complexity of primary, seminal, and crown roots highlight root type-specific functional diversity in maize (Zea mays L.)

Maize develops a complex root system composed of embryonic and post-embryonic roots. Spatio-temporal differences in the formation of these root types imply specific functions during maize development. A comparative transcriptomic study of embryonic primary and seminal, and post-embryonic crown roots of the maize inbred line B73 by RNA sequencing along with anatomical studies were conducted early in development. Seminal roots displayed unique anatomical features, whereas the organization of primary and crown roots was similar. For instance, seminal roots displayed fewer cortical cell files and their stele contained more meta-xylem vessels. Global expression profiling revealed diverse patterns of gene activity across all root types and highlighted the unique transcriptome of seminal roots. While functions in cell remodeling and cell wall formation were prominent in primary and crown roots, stress-related genes and transcriptional regulators were over-represented in seminal roots, suggesting functional specialization of the different root types. Dynamic expression of lignin biosynthesis genes and histochemical staining suggested diversification of cell wall lignification among the three root types. Our findings highlight a cost-efficient anatomical structure and a unique expression profile of seminal roots of the maize inbred line B73 different from primary and crown roots

Periodic Health Examinations and Missed Opportunities among Patients Likely Needing Mental Health Care

Periodic health examinations (PHEs) are the most common reason adults see primary care providers. It is unknown if PHEs serve as a "safe portal" for patients with mental health needs to initiate care. We examined how physician communication styles impact mental health service delivery in PHEs

Viral Kinetics of Sequential SARS-CoV-2 Infections

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11th, 2020, and July 28th, 2022. We compared the SARS-CoV-2 viral kinetics of first vs. second infections in this group, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a faster clearance time. Furthermore, a person\u27s relative (rank-order) viral clearance time, compared to others infected with the same variant, was roughly conserved across first and second infections, so that individuals who had a relatively fast clearance time in their first infection also tended to have a relatively fast clearance time in their second infection (Spearman correlation coefficient: 0.30, 95% credible interval (0.12, 0.46)). These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person\u27s relative ability to clear SARS-CoV-2 infection that persists across sequential infections

A dosimetric analysis of the aeroformTM tissue expander in radiation therapy

Purpose: The aim of this study is to evaluate the effects of the metallic reservoir and the use of gas within the Aeroform™ tissue expander with respect to the radiation dose distribution.Methods: Dosimetric effects of using a metallic reservoir within a breast tissue expander during external beam radiotherapy were investigated. To view the internal components of the reservoir, it was removed from the tissue expander and imaged on a Varian AS500 electronic portal imager. To calculate the relative density of each component within the reservoir, an ionization chamber within solid water was used to measure the dose and compared to a simulation within the Pinnacle treatment planning system (TPS). To examine the relative dose profile along the length of the reservoir, the reservoir was exposed on EBT3 film and analyzed using SNC Patient™. In-vivo Dosimetry was performed using a RANDO® Woman phantom. Thermo-luminescent dosimeters were placed within the wax bolus enveloping the tissue expander.Results: Imaging the reservoir on the electronic portal imager revealed it consists of 3 distinct components. The densities assigned in the TPS, which resulted in calculated doses which matched the measured doses were; Section 1 = 0 g/cm3, Section 2 = 2.8 g/cm3 and Section 3 = 0.7 g/cm3. Relative dose reductions were observed due to the metallic case; Section 1 = 20%, Section 2 = 40% and Section 3 = 30%. Entrance doses ranged from 2.39 - 2.53 Gy for both the medial and lateral beams. Exit doses ranging from 1.10 - 1.71 Gy were observed in both beams. There was a significant difference in measured and calculated doses at exit locations in the beam.Conclusion: Dosimetric effects due to the metallic reservoir within the Aeroform breast tissue expander have been demonstrated and have been observed to be significant. To increase the dosimetric accuracy when contouring, individual components of the reservoir should be distinguished. Our in-vivo experiment showed that dose homogeneity was difficult due to the metallic reservoir and we recommend stringent patient dose monitoring when using this expander during radiotherapy.-----------------------------Cite this article as: Tran T, Ding W, Subramanian B, Melven L, Chao M, Farrow H, Baker C. A dosimetric analysis of the aeroformTM tissue expander in radiation therapy. Int J Cancer Ther Oncol 2014; 2(3):020316. DOI: 10.14319/ijcto.0203.1

Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Series From a 12-Month Longitudinal Occupational Cohort

Findings are described in 7 patients with severe acute respiratory syndrome coronavirus 2 reinfection from the National Basketball Association 2020-2021 occupational testing cohort, including clinical details, antibody test results, genomic sequencing, and longitudinal reverse-transcription polymerase chain reaction results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response

Obesity and the Microvasculature: A Systematic Review and Meta-Analysis

10.1371/journal.pone.0052708PLoS ONE82

Enclosing a pen reduced time to response to questionnaire mailings

OBJECTIVES: To assess the effectiveness of including a pen in postal questionnaires on response rate, necessity of reminders, time to response, and completeness of response to the primary outcome question (POQ).   STUDY DESIGN AND SETTING: A two-arm randomized controlled trial (RCT) embedded within the screening of older women for prevention of fracture trial (SCOOP). Women, aged 70-75 years, were randomized to receive a pen with their questionnaire (n = 3,826) or to receive the questionnaire alone (n = 3,829). The results were combined with another embedded RCT in a meta-analysis.   RESULTS: A response rate of 92.4% was observed in the pen group compared with 91.3% in the control group (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 0.98, 1.37; P = 0.08). There was a difference in reminders required (OR = 0.88; 95% CI: 0.79, 0.98; P = 0.02), time to response (hazard ratio = 1.06; 95% CI: 1.01, 1.11; P = 0.01) and some difference in the completeness of response to the POQ (OR = 1.18; 95% CI: 1.00, 1.39; P = 0.05). The pooled OR from the meta-analysis for response rate was 1.21 (95% CI: 1.05, 1.39; P = 0.01).   CONCLUSION: Inclusion of a pen with postal questionnaires potentially has a positive impact on response rates and the number of reminders required. There may be some reduction in time to response. Studies of different participant groups are needed to test the effectiveness over more diverse populations