Physician Perceptions on Cancer Screening for LGBTQ+ Patients.

The LGBTQ+ community experiences cancer disparities due to increased risk factors and lower screening rates, attributable to health literacy gaps and systemic barriers. We sought to understand the experiences, perceptions, and knowledge base of healthcare providers regarding cancer screening for LGBTQ+ patients. A 20-item IRB-approved survey was distributed to physicians through professional organizations. The survey assessed experiences and education regarding the LGBTQ+ community and perceptions of patient concerns with different cancer screenings on a 5-point Likert scale. Complete responses were collected from 355 providers. Only 100 (28%) reported past LGBTQ+-related training and were more likely to be female (p = 0.020), have under ten years of practice (p = 0.014), or practice family/internal medicine (p < 0.001). Most (85%) recognized that LGBTQ+ subpopulations experience nuanced health issues, but only 46% confidently understood them, and 71% agreed their clinics would benefit from training. Family/internal medicine practitioners affirmed the clinical relevance of patients' sexual orientation (94%; 62% for medical/radiation oncology). Prior training affected belief in the importance of sexual orientation (p < 0.001), confidence in understanding LGBTQ+ health concerns (p < 0.001), and willingness to be listed as "LGBTQ+-friendly" (p = 0.005). Our study suggests that despite a paucity of formal training, most providers acknowledge that LGBTQ+ patients have unique health needs. Respondents had a lack of consensus regarding cancer screenings for lesbian and transgender patients, indicating the need for clearer screening standards for LGBTQ+ subpopulations and educational programs for providers.

PRAME immunohistochemistry is useful in differentiating oral melanomas from nevi and melanotic macules.

BACKGROUND: Oral melanocytic neoplasms pose a diagnostic challenge to pathologists owing to their rarity relative to those in the skin. The utility of PRAME in distinguishing nevi from melanomas has been established in the skin, but limited information exists regarding its usefulness in the oral cavity. METHODS: Thirty-five previously diagnosed pigmented oral lesions were retrospectively evaluated with PRAME. The lesions consisted of 16 oral nevi, 10 melanomas, and 10 melanotic macules. RESULTS: Strong and diffuse nuclear PRAME staining was observed in all but one of the oral melanomas, which showed no staining. No nuclear PRAME staining was observed in any of the oral nevi or melanotic macules. CONCLUSIONS: PRAME is a useful tool in the evaluation of oral melanocytic neoplasms. Our data indicate that PRAME is a highly specific but incompletely sensitive marker of oral melanoma. Larger studies could further illuminate the diagnostic value of PRAME in oral lesions.

Perceptions of and barriers to cancer screening by the sexual and gender minority community: a glimpse into the health care disparity.

PURPOSE: A disparity exists in cancer screening rates for the Sexual and Gender Minority (SGM) community. We sought to understand the perceptions and baseline knowledge of cancer screening among SGM community members. METHODS: Survey administered via social media from June 2018 to October 2018. We asked 31 questions focused on cancer screening, human papillomavirus, emotional distress, and experience with the health care system. Those included were 18 years or older. Cancer screening attitudes and knowledge, as well as perceptions of the health care system were investigated. RESULTS: There were 422 respondents analyzed: 24.6% identified as female, 25.5% as male, 40.1% transgender, and 9.6% as other. 65.4% of the SGM community is not certain what cancer screening to do for themselves. Only 27.3% and 55.7% knew that HPV was a risk factor associated with head and neck cancer and anal cancer, respectively. Half stated their emotional distress prevents them from getting cancer screening. It was identified that process changes in making appointments, comforts during the visit, and formal training for physicians and nurses could increase cancer screening compliance for this community. The transgender population had a trend in more gaps in knowledge of appropriate cancer screening and significant excess emotional distress. CONCLUSION: Gaps in cancer screening knowledge and emotional and financial distress may be responsible for the disparity of lower cancer screening rates for the SGM population and the transgender population may be most at risk. Appreciating the cancer screening concerns of the SGM population can help shape future clinical and institutional approaches to improve health care delivery.

A Pilot Trial Using Telemedicine in Radiation Oncology: The Future of Health Care Is Virtual.

Background: Social determinants of health directly affect cancer survival. Driven by advances in technology and recent demands due to COVID-19, telemedicine has the ability to improve patient access to care, lower health care costs, and increase workflow efficiency. The role of telemedicine in radiation oncology is not established. Materials and Methods: We conducted an IRB-approved pilot trial using a telehealth platform for the first post-radiation visit in patients with any cancer diagnosis. The primary endpoint was feasibility of using telehealth defined by completion of five telehealth visits per month in a single department. Secondary endpoints included the ability to assess patients appropriately, patient and physician satisfaction. Physicians were surveyed again during the pandemic to determine whether viewpoints changed. Results: Between May 27, 2016 and August 1, 2018, 37 patients were enrolled in the Telehealth in Post-operative Radiation Therapy (TelePORT) trial, with 24 evaluable patients who completed their scheduled telehealth visit. On average, 1.4 patients were accrued per month. All patients were satisfied with their care, had enough time with their physician and 85.7% believed the telehealth communication was excellent. All physicians were able to accurately assess the patient's symptoms via telehealth, whereas 82.3% felt they could accurately assess treatment-related toxicity. Physicians assessing skin toxicity from breast radiation were those who did not feel they were able to assess toxicity. Discussion and Conclusions: Both health care providers and patients have identified telemedicine as a suitable platform for radiation oncology visits. Although there are limitations, telemedicine has significant potential for increasing access of cancer care delivery in radiation oncology.

Restoring the DREAM Complex Inhibits the Proliferation of High-Risk HPV Positive Human Cells.

High-risk (HR) human papillomaviruses are known causative agents in 5% of human cancers including cervical, ano-genital and head and neck carcinomas. In part, HR-HPV causes cancer by targeting host-cell tumor suppressors including retinoblastoma protein (pRb) and RB-like proteins p107 and p130. HR-HPV E7 uses a LxCxE motif to bind RB proteins, impairing their ability to control cell-cycle dependent transcription. E7 disrupts DREAM (Dimerization partner, RB-like, E2F and MuvB), a transcriptional repressor complex that can include p130 or p107, but not pRb, which regulates genes required for cell cycle progression. However, it is not known whether disruption of DREAM plays a significant role in HPV-driven tumorigenesis. In the DREAM complex, LIN52 is an adaptor that binds directly to p130 via an E7-like LxSxE motif. Replacement of the LxSxE sequence in LIN52 with LxCxE (LIN52-S20C) increases p130 binding and partially restores DREAM assembly in HPV-positive keratinocytes and human cervical cancer cells, inhibiting proliferation. Our findings demonstrate that disruption of the DREAM complex by E7 is an important process promoting cellular proliferation by HR-HPV. Restoration of the DREAM complex in HR-HPV positive cells may therefore have therapeutic benefits in HR-HPV positive cancers.

Onco-metabolism: defining the prognostic significance of obesity and diabetes in women with brain metastases from breast cancer.

PURPOSE: Metabolic dysregulation has been implicated as a molecular driver of breast cancer in preclinical studies, especially with respect to metastases. We hypothesized that abnormalities in patient metabolism, such as obesity and diabetes, may drive outcomes in breast cancer patients with brain metastases. METHODS: We retrospectively identified 84 consecutive patients with brain metastases from breast cancer treated with intracranial radiation therapy. Radiation was delivered as whole-brain radiation to a median dose of 3000 cGy or stereotactic radiosurgery to a median dose of 2100 cGy. Kaplan Meier curves were generated for overall survival (OS) data and Mantel-Cox regression was performed to detect differences in groups. RESULTS: At analysis, 81 survival events had occurred and the median OS for the entire cohort was 21.7 months. Despite similar modified graded prognostic assessments, resection rates, and receptor status, BMI ≥ 25 kg/m2 (n = 45) was associated with decreased median OS (13.7 vs. 30.6 months; p < 0.001) and median intracranial progression-free survival (PFS) (7.4 vs. 10.9 months; p = 0.04) compared to patients with BMI < 25 kg/m2 (n = 39). Similar trends were observed among all three types of breast cancer. Patients with diabetes (n = 17) had decreased median OS (11.8 vs. 26.2 months; p < 0.001) and median intracranial PFS (4.5 vs. 10.3 months; p = 0.001) compared to non-diabetics (n = 67). On multivariate analysis, both BMI ≥ 25 kg/m2 [HR 2.35 (1.39-3.98); p = 0.002] and diabetes [HR 2.77 (1.454-5.274); p = 0.002] were associated with increased mortality. CONCLUSIONS: Elevated BMI or diabetes may negatively impact both overall survival and local control in patients with brain metastases from breast cancer, highlighting the importance of the translational development of therapeutic metabolic interventions. Given its prognostic significance, BMI should be used as a stratification in future clinical trial design in this patient population.

Caloric restriction counteracts chemotherapy-induced inflammation and increases response to therapy in a triple negative breast cancer model.

Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model. Chemotherapy can induce inflammation that breeds resistance to therapy. We propose CR as a mechanism to decrease chemotherapy-induced inflammation and increase efficacy of therapy. 12-week old Balb/c mice were orthotopically injected with a syngeneic triple negative breast cancer cell line (4T1) and were treated in one of six cohorts: ad lib fed (AL), 30% reduction in calorie intake (CR), cisplatin or docetaxol alone or a combination CR+cisplatin/docetaxol. Mice in the cohorts receiving chemotherapy+CR had longer overall survival (12 ± 2 days) as compared to the AL group. These mice also demonstrated less lung metastases at the final time point of in vivo imaging. In addition, downregulation of the IGF-1R and IRS signaling pathways were noted most significantly in those mice receiving combination therapy. Lastly, serum from these mice demonstrated an increase in inflammatory cytokines TNF-α and IL-1ß in response to chemotherapy alone. This increase was dampened by the addition of CR. Taken together, these data suggest that while chemotherapy is effective in TNBC, it can cause inflammation, which can be a driver of resistance to therapy. This chemotherapy-induced inflammation can be reversed with the use of CR as a nontoxic adjunct to treatment.

Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element.

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

Prenatal diagnosis and molecular cytogenetic characterization of rec(10)dup(10p)inv(10)(p11.2q26.3) in a fetus associated with paternal pericentric inversion.

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a recombinant chromosome 10 in a fetus associated with a paternal pericentric inversion. CASE REPORT: A 35-year-old woman underwent amniocentesis at 18 weeks of gestation because of an advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,der(10)del(10) (q26.3)dup(10)(p11.2p15). She underwent repeat amniocentesis at 21 weeks of gestation and array comparative genomic hybridization revealed a 31.65-Mb duplication of chromosome 10p15.3-p11.22 and a 3.07-Mb deletion of chromosome 10q26.3. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling and cytogenetic analysis revealed a karyotype of 46,XY,inv(10)(p11.2q26.3) in the father and a karyotype of 46,XX in the mother. The pregnancy was subsequently terminated, and a fetus was delivered with prominent facial dysmorphism. Postnatal cytogenetic analysis of the placenta revealed a karyotype of 46,XY, rec(10)dup(10p)inv(10)(p11.2q26.3). Fluorescence in situ hybridization analysis revealed a duplication of terminal 10p and a deletion of terminal 10q in the recombinant chromosome 10. Array comparative genomic hybridization analysis of the cord blood and umbilical cord confirmed the prenatal diagnosis. CONCLUSION: Prenatal diagnosis of a recombinant chromosome because of an advanced maternal age should alert the possibility of a paternal pericentric inversion.

Prenatal diagnosis of partial monosomy 5p (5p15.1→pter) and partial trisomy 7p (7p15.2→pter) associated with cystic hygroma, abnormal skull development, and ventriculomegaly.

OBJECTIVE: Prenatal diagnosis of concomitant chromosome 5p deletion syndrome and chromosome 7p duplication syndrome in a fetus with abnormal prenatal ultrasound is presented. CASE REPORT: A 34-year-old woman was referred for amniocentesis at 22 weeks of gestation because of an irregular-shaped skull, bilateral ventriculomegaly, and nuchal cystic hygroma. Amniocentesis revealed a derivative chromosome 5 with a distal 5p deletion and an addendum of an extra unknown chromosomal segment at the breakpoint of 5p. Cytogenetic analysis of parental bloods revealed a karyotype of 46, XX, t(5;7)(p15.1;p15.2) in the mother and a karyotype of 46,XY in the father. The karyotype of the fetus was 46, XX, der(5) t(5;7)(p15.1;p15.2)mat consistent with partial monosomy 5p (5p15.1→pter) and partial trisomy 7p (7p15.2→pter). A malformed fetus was subsequently delivered with an irregular-shaped skull, a large anterior fontanelle, brachycephaly, hypertelorism, a high and prominent forehead, a large nuchal cystic hygroma, large low-set ears, a short and flattened nose, and micrognathia. Array comparative genomic hybridization analysis of the placenta revealed the result of arr 5p15.33p15.1 (22,179-18,133,327)×1.0, 7p22.3p15.2 (54,215-25,551,540)×3.0, indicating an 18.11-Mb deletion of 5p (5p15.33-p15.1) and a 22.5-Mb duplication of 7p (7p22.3-p15.2). Cord blood sampling revealed a karyotype of 46, XX, der(5)t(5;7) (p15.1;p15.2)mat. CONCLUSION: Fetuses with 5p deletion syndrome and 7p duplication syndrome may present ventriculomegaly, abnormal skull development, and cystic hygroma on prenatal ultrasound.

Undergraduate geriatric education through community service learning.

INTRODUCTION: Despite the exponential growth of the elderly population worldwide, geriatric education has been a formal component of only a few dental schools' curricula. OBJECTIVE: To describe the geriatric community service learning (CSL) component of the professionalism and community service (PACS) module, and to explore a CSL project carried out by a group of first year dental students at a long-term care facility. METHODS: A literature review was performed to present and describe the CSL component of the PACS module. Students' personal reflections were used to illustrate some of the joys and challenges of experiencing a long-term care facility environment. RESULTS: The newly developed PACS module combines community service learning with the long-term care experience. Students develop, apply and evaluate an educational health promotion activity in a long-term care facility. CONCLUSIONS: The PACS module has encouraged students to acquire comprehensive knowledge and awareness of the needs and dynamics of a long-term care as they collaboratively interacted with personnel from the facility to develop their projects. The authors would like to engage other schools in discussing the need to integrate community-based geriatric education into their dental curricula.

SARANA: language, compiler and run-time system support for spatially aware and resource-aware mobile computing.

Increasingly, spatial awareness plays a central role in many distributed and mobile computing applications. Spatially aware applications rely on information about the geographical position of compute devices and their supported services in order to support novel functionality. While many spatial application drivers already exist in mobile and distributed computing, very little systems research has explored how best to program these applications, to express their spatial and temporal constraints, and to allow efficient implementations on highly dynamic real-world platforms. This paper proposes the SARANA system architecture, which includes language and run-time system support for spatially aware and resource-aware applications. SARANA allows users to express spatial regions of interest, as well as trade-offs between quality of result (QoR), latency and cost. The goal is to produce applications that use resources efficiently and that can be run on diverse resource-constrained platforms ranging from laptops to personal digital assistants and to smart phones. SARANA's run-time system manages QoR and cost trade-offs dynamically by tracking resource availability and locations, brokering usage/pricing agreements and migrating programs to nodes accordingly. A resource cost model permeates the SARANA system layers, permitting users to express their resource needs and QoR expectations in units that make sense to them. Although we are still early in the system development, initial versions have been demonstrated on a nine-node system prototype.