Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making

Side Effects to Systemic Glucocorticoid Therapy in Dogs Under Primary Veterinary Care in the UK

Objectives: Systemic glucocorticoids are widely used in companion animals. This study aimed to estimate the frequency, describe the characteristics and to evaluate risk factors for common side effects to systemic glucocorticoid therapy in dogs under primary veterinary care in the UK. Methods: A cohort study using VetCompassTM data from 455,557 dogs under primary veterinary care during 2013 estimated the frequency of side effects to systemic glucocorticoid therapy occurring within 31 days of therapy. Risk factors for the most common side effects, polyuria and polydipsia (PUPD), were evaluated using multivariable logistic regression modeling (P < 0.05). Results: During 2013, 28,472 study dogs received systemic glucocorticoids (6.2%, 95% CI 6.2–6.3). Review of the records of 3,000 randomly selected treated dogs identified 148 (4.9%, 95% CI 4.2–5.7%) dogs with at least one side effect recorded within 31 days of therapy. The most frequent side effects were polydipsia (39.2% of total presenting signs), polyuria (28.4%), vomiting (16.2%) and diarrhea (14.9%), dogs receiving only oral systemic glucocorticoids (odds ratio, OR: 3.72) and dogs receiving both oral and injectable systemic glucocorticoid (OR: 10.71) had increased odds of PUPD compared with dogs receiving only injectable systemic glucocorticoid. Focusing on the active substance used, treatment with prednisolone tablets only (OR: 3.53) and treatment with both prednisolone tablets and injectable dexamethasone sodium phosphate (OR: 7.62) showed increased odds of PUPD compared to treatment with injectable dexamethasone sodium phosphate only. Brief: These results can assist veterinarians to optimize therapeutic selection for reduced side effect, to inform owners on common side effects, and help protect the welfare of pets and their owners

Foodborne Transmission of Bovine Spongiform Encephalopathy to Nonhuman Primates

Risk for human exposure to bovine spongiform encephalopathy (BSE)–inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7–5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7–10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Final report - A Roadmap for Open Education in Switzerland

This report is the main output of a scientific exchange among a group of 10 Swiss and International scholars who have been drafting a roadmap for Open Education in the Swiss Higher Education landscape. The roadmap is organised around 3 main strategic focuses and each focus is detailed in 4 actions: i) Focus 1: Broad horizon education; ii) Focus 2: Ethical and responsible use of technology; and iii) Focus 3: Humans reconnected to the planet’s ecosystem. This work stems from i) a Delphi study with worldwide Open Education experts; ii) two workshops held during Open Education events – the Open Education Global Conference and the Swiss Open Education Day; iii) 9 months of work and, iv) a vision exercice, projecting the kind of education we would like in 50 years. Stakeholders, citizens and communities are invited to join and actively contribute to the discussion through the interactive version of the roadmap, https://edutechwiki.unige.ch/en/Open_Education_Roadmap . </p

Exposure to overhead high-voltage power lines and childhood leukemia risk: an Italian population-based case-control study

Background Previous epidemiologic findings suggest a positive association between magnetic field exposure induced by high voltage power lines and childhood leukemia (CL). Contrasting results are still reported, possibly biased by exposure misclassification, relying on different assessment methods across studies, and by unmeasured confounders. Methods/Approach We further studied this relation in the Modena and Reggio Emilia provinces (Northern Italy), and through a modelling exposure assessment we identified the corridors along high voltage power lines with magnetic field intensity in the 0.1-0.4 µT ranges. Then we identified 182 cases of newly-diagnosed CL within these provinces from 1998 to 2019. We sampled four age-, sex-, province of residence- and calendar year- matched controls for each case. We computed the odds ratio (OR) and its 95% confidence interval (CI) of CL in a conditional logistic regression analysis according to distance between home address at the time of diagnosis of the case and the nearest high voltage power line and also to residential magnetic field modeled intensity. Results OR of CL was 0.9 (95% CI 0.5-1.6), 0.9 (95% CI 0.4-2.0), 1.5 (95% CI 0.5-4.7) and 4.0 (95% CI 1.0-16.0) for children living respectively 200-400 m, 100-200 m, 50-100 m, and less than 50 m from the nearest high voltage power line compared to those residing further than 400 m. OR of CL associated with residence in the area with exposure &gt;0.1 µT was 8.0 (95% CI 0.7-88.2). Conclusions Though the number of exposed children in this study was too low to allow firm conclusions, yielding in such cases high but very imprecise estimates, our results seem more suggestive of an excess risk of leukemia among children living close to electric power lines or exposed to higher magnetic fields intensity

Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

Abstract HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making