Impaired hypoglycaemia awareness in early pregnancy increases risk of severe hypoglycaemia in the mid-long term postpartum irrespective of breastfeeding status in women with type 1 diabetes

Information regarding the postpartum period in women with type 1 diabetes (T1D) is scarce. We aim to evaluate the relation of impaired hypoglycaemia awareness (IAH) in early pregnancy and breastfeeding status (its presence and duration) with severe postpartum hypoglycaemia (SH).Retrospective cohort study of women with T1D followed during pregnancy between 2012 and 2019. Data on SH were recorded before and during pregnancy. IAH was evaluated at the first antenatal visit. Data on breastfeeding and the long-term postpartum period were collected by questionnaire and from medical records.A total of 89 women with T1D were included with a median follow-up after pregnancy of 19.2 [8.7-30.5] months. Twenty-eight (32%) women had IAH at the first antenatal visit. At discharge, 74 (83%) started breastfeeding during a median of 8 [4.4-15] months. A total of 18 (22%) women experienced ≥1 SH during postpartum. The incidence of SH significantly increased from pregestational to the gestational and post-partum period (0.09, 0.15 and 0.25 episodes/patient-year, respectively). Postpartum SH rates were comparable in breastfeeding and non-breastfeeding women (21.4% vs. 25%, respectively, p>0.05). Clarke test score at the first antenatal visit was associated with postpartum SH (for each 1-point increase: OR 1.53; 95% CI, 1.06-2.21) adjusted for confounders. No other diabetes and pregnancy-related variables were identified as predictors of SH in this period.SH are common in the long-term postpartum period independently of breastfeeding. Assessing IAH in early pregnancy could identify those at an increased risk of SH in the postpartum period.Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved

Calcium and temperature effect on structural damage of hot air dried apple slices: Nonlinear irreversible thermodynamic approach and rehydration analysis

Mathematical models traditionally employed in fitting convective drying data do not use to report information about chemical and other physical changes different from the simple decrease in moisture content. In the present study, structural damage undergone by fresh and vacuum impregnated apple slices with different calcium lactate concentrations during convective drying at 30, 40 and 50 °C was analysed by applying equations derived from nonlinear irreversible thermodynamics to experimental data. According to the results obtained, vacuum impregnation with isotonic sucrose solution before drying at 30 °C provided maximum protection to cellular structure by promoting reversible deformations against irreversible breakages. On the contrary, cell walls strengthen with calcium had severe damaged during drying. Regarding air temperature, it was directly related both to the molar energy employed in deforming structures and the drying rate. These results were confirmed by analysing dried samples behaviour during further rehydration.Barrera Puigdollers, C.; Betoret Valls, N.; Betoret Valls, ME.; Fito Maupoey, P. (2016). Calcium and temperature effect on structural damage of hot air dried apple slices: Nonlinear irreversible thermodynamic approach and rehydration analysis. Journal of Food Engineering. 189:106-114. doi:10.1016/j.jfoodeng.2016.05.024S10611418

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®.

Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2- breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (rc(RS) = 0.96, 95% CI 0.93-0.97 with level of agreement (LoA) of -7.69 to 8.12; rc(EP) = 0.97, 95% CI 0.96-0.98 with LoA of -0.64 to 1.26 and rc(ROR) = 0.97 (95% CI 0.94-0.98) with LoA of -8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data

Enhancing physicians’ radiology diagnostics of COVID-19’s effects on lung health by leveraging artificial intelligence

Introduction: This study aimed to develop an individualized artificial intelligence model to help radiologists assess the severity of COVID-19's effects on patients' lung health.Methods: Data was collected from medical records of 1103 patients diagnosed with COVID-19 using RT- qPCR between March and June 2020, in Hospital Madrid-Group (HM-Group, Spain). By using Convolutional Neural Networks, we determine the effects of COVID-19 in terms of lung area, opacities, and pulmonary air density. We then combine these variables with age and sex in a regression model to assess the severity of these conditions with respect to fatality risk (death or ICU).Results: Our model can predict high effect with an AUC of 0.736. Finally, we compare the performance of the model with respect to six physicians' diagnosis, and test for improvements on physicians' performance when using the prediction algorithm.Discussion: We find that the algorithm outperforms physicians (39.5% less error), and thus, physicians can significantly benefit from the information provided by the algorithm by reducing error by almost 30%

No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations

Background: germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9. Considering the potential implications of the finding, we undertook the task of validating the initial results in this study. Methods: allele-specific expression was measured using the highly quantitative and robust technique of pyrosequencing. Individuals from two different populations were studied, one Caucasian-dominated and the other of Ashkenazi Jewish descent, with different sources of non-tumoral genetic material in each. Results: our results showed no statistically significant differences in the degree of ASE between CRC patients and controls, considering ASE as either a quantitative or a binary trait. Using defined cutoff values to categorise ASE, 1.0% of blood lymphocytes from informative Israeli cases (total n=96) were ASE positive (median 1.00; range 0.76-1.31) and 2.2% of informative matched controls (total n=90) were ASE positive (median 1.00; range 0.76-1.87). Likewise, normal mucosae from Spanish patients (median 1.03; range: 0.68-1.43; n=75) did not show significant differences in the degree of ASE when compared with the Israeli patients or controls. Conclusions: taken together, these results suggest that ASE of TGFBR1 does not confer an increased risk of CRC

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM “El Álamo III” retrospective study

Purpose: To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. Methods: a retrospective analysis was conducted from 10, 638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry “El Álamo III”, dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. Results: 7, 641 patients were evaluable. Of them, 2, 252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. Conclusions: Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors

SUMOylation inhibition mediated by disruption of SUMO E1-E2 interactions confers plant susceptibility to necrotrophic fungal pathogens

Protein modification by SUMO modulates essential biological processes in eukaryotes. SUMOylation is facilitated by sequential action of the E1-activating, E2-conjugating, and E3-ligase enzymes. In plants, SUMO regulates plant development and stress responses, which are key determinants in agricultural productivity. To generate additional tools for advancing our knowledge about the SUMO biology, we have developed a strategy for inhibiting in vivo SUMO conjugation based on disruption of SUMO E1-E2 interactions through expression of E1 SAE2UFDCt domain. Targeted mutagenesis and phylogenetic analyses revealed that this inhibition involves a short motif in SAE2UFDCt highly divergent across kingdoms. Transgenic plants expressing the SAE2UFDCt domain displayed dose-dependent inhibition of SUMO conjugation, and have revealed the existence of a post-transcriptional mechanism that regulates SUMO E2 conjugating enzyme levels. Interestingly, these transgenic plants displayed increased susceptibility to necrotrophic fungal infections by Botrytis cinerea and Plectosphaerella cucumerina. Early after fungal inoculation, host SUMO conjugation was post-transcriptionally downregulated, suggesting that targeting SUMOylation machinery could constitute a novel mechanism for fungal pathogenicity. These findings support the role of SUMOylation as a mechanism involved in plant protection from environmental stresses. In addition, the strategy for inhibiting SUMO conjugation in vivo described in this study might be applicable in important crop plants and other non-plant organisms regardless of their genetic complexity

Predicting response and survival in chemotherapy-treated triple-negative breast cancer

In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not