Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer.

BACKGROUND: The addition of pembrolizumab to neoadjuvant chemotherapy led to a significantly higher percentage of patients with early triple-negative breast cancer having a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery in an earlier analysis of this phase 3 trial of neoadjuvant and adjuvant therapy. The primary results regarding event-free survival in this trial have not been reported. METHODS: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response (the results for which have been reported previously) and event-free survival, defined as the time from randomization to the date of disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause. Safety was also assessed. RESULTS: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. The median follow-up at this fourth planned interim analysis (data cutoff, March 23, 2021) was 39.1 months. The estimated event-free survival at 36 months was 84.5% (95% confidence interval [CI], 81.7 to 86.9) in the pembrolizumab-chemotherapy group, as compared with 76.8% (95% CI, 72.2 to 80.7) in the placebo-chemotherapy group (hazard ratio for event or death, 0.63; 95% CI, 0.48 to 0.82; P<0.001). Adverse events occurred predominantly during the neoadjuvant phase and were consistent with the established safety profiles of pembrolizumab and chemotherapy. CONCLUSIONS: In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).

SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes.

Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.

Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma.

OBJECTIVES: This study aimed to explore the practical organisational aspects and difficulties in the implementation of the molecular classification of endometrial carcinoma (EC), and to demonstrate its potential impact in prognostic risk group classification. METHODS: We conducted a multicentre, retrospective cohort study of 230 patients with EC diagnosed between 2019 and 2022. Sample processing, clinicopathological, treatment and follow-up data were collected. Molecular classification was obtained by p53 and mismatch repair proteins immunohistochemistry, and POLE next-generation sequencing. RESULTS: Implementation was achieved through centralization of molecular analysis. In practice, it was possible to optimise turnaround times of complete integrative reports for hysterectomy specimens to a median time of 18 workdays. If genetic study was started in endometrial biopsies before surgery, 82.0% were available at the time of multidisciplinary tumour board, compared to 8.4% if performed in hysterectomy. ECs were classified as follows: 37.8% no specific molecular profile, 31.7% p53 abnormal, 24.3% mismatch repair deficient, and 6.1% POLE mutant. Integration of these results with traditional clinicopathologic factors led to a change in prognostic risk group in 15 (6.5%) patients, most being initially allocated to high-intermediate (n = 8) and low (n = 5) risk groups. Eight patients changed to a higher risk, and 7 to a lower risk group, whereas 2 remained in the same group. CONCLUSIONS: Centralization of EC molecular classification is a feasible option for countries with limited resources. Optimization of workflows may be achieved by earlier analysis in biopsies and prioritisation of patients whose results imply changes in risk group classification.

Combined loss of CDH1 and downstream regulatory sequences drive early-onset diffuse gastric cancer and increase penetrance of hereditary diffuse gastric cancer.

BACKGROUND: Germline CDH1 pathogenic or likely pathogenic variants cause hereditary diffuse gastric cancer (HDGC). Once a genetic cause is identified, stomachs' and breasts' surveillance and/or prophylactic surgery is offered to asymptomatic CDH1 carriers, which is life-saving. Herein, we characterized an inherited mechanism responsible for extremely early-onset gastric cancer and atypical HDGC high penetrance. METHODS: Whole-exome sequencing (WES) re-analysis was performed in an unsolved HDGC family. Accessible chromatin and CDH1 promoter interactors were evaluated in normal stomach by ATAC-seq and 4C-seq, and functional analysis was performed using CRISPR-Cas9, RNA-seq and pathway analysis. RESULTS: We identified a germline heterozygous 23 Kb CDH1-TANGO6 deletion in a family with eight diffuse gastric cancers, six before age 30. Atypical HDGC high penetrance and young cancer-onset argued towards a role for the deleted region downstream of CDH1, which we proved to present accessible chromatin, and CDH1 promoter interactors in normal stomach. CRISPR-Cas9 edited cells mimicking the CDH1-TANGO6 deletion display the strongest CDH1 mRNA downregulation, more impacted adhesion-associated, type-I interferon immune-associated and oncogenic signalling pathways, compared to wild-type or CDH1-deleted cells. This finding solved an 18-year family odyssey and engaged carrier family members in a cancer prevention pathway of care. CONCLUSION: In this work, we demonstrated that regulatory elements lying down-stream of CDH1 are part of a chromatin network that control CDH1 expression and influence cell transcriptome and associated signalling pathways, likely explaining high disease penetrance and very young cancer-onset. This study highlights the importance of incorporating scientific-technological updates and clinical guidelines in routine diagnosis, given their impact in timely genetic diagnosis and disease prevention.

NGS Data Repurposing Allows Detection of tRNA Fragments as Gastric Cancer Biomarkers in Patient-Derived Extracellular Vesicles.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

A review in radiomics: Making personalized medicine a reality via routine imaging.

Radiomics is the quantitative analysis of standard-of-care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or predictive models. Radiomics analysis can be performed by extracting hand-crafted radiomics features or via deep learning algorithms. Radiomics has evolved tremendously in the last decade, becoming a bridge between imaging and precision medicine. Radiomics exploits sophisticated image analysis tools coupled with statistical elaboration to extract the wealth of information hidden inside medical images, such as computed tomography (CT), magnetic resonance (MR), and/or Positron emission tomography (PET) scans, routinely performed in the everyday clinical practice. Many efforts have been devoted in recent years to the standardization and validation of radiomics approaches, to demonstrate their usefulness and robustness beyond any reasonable doubts. However, the booming of publications and commercial applications of radiomics approaches warrant caution and proper understanding of all the factors involved to avoid "scientific pollution" and overly enthusiastic claims by researchers and clinicians alike. For these reasons the present review aims to be a guidebook of sorts, describing the process of radiomics, its pitfalls, challenges, and opportunities, along with its ability to improve clinical decision-making, from oncology and respiratory medicine to pharmacological and genotyping studies.

Hybrid sensor based on a hollow square core fiber for temperature independent refractive index detection.

In this work, a hybrid sensor based on a section of hollow square core fiber (HSCF) spliced between two single mode fibers is proposed for the measurement of refractive index of liquids. The sensor, with a length of a few millimeters, operates in a transmission configuration. Due to the HSCF inner geometry, two different interferometers are generated. The first, a Mach-Zehnder interferometer, is insensitive to the external refractive index, and presents a sensitivity to temperature of (29.2 ± 1.1) pm/°C. The second one, a cladding modal interferometer, is highly sensitive to the external refractive index. An experimental resolution of 1.0 × 10-4 was achieved for this component. Due to the different responses of each interferometer to the parameters under study, a compensation method was developed to attain refractive index measurements that are temperature independent. The proposed sensor can find applications in areas where refractive index measurements are required and the control of room temperature is a challenge, such as in the food and beverage industry, as well as in biochemical or biomedical industries.

Simultaneous measurement of displacement and temperature using a balloon-like hybrid fiber sensor.

A fiber sensor based on a silica capillary in a balloon-like shape for simultaneous measurement of displacement and temperature is proposed and experimentally demonstrated. The sensor is fabricated by splicing a segment of a hollow-core fiber between two single-mode fibers (SMF) and by creating a balloon shape with the capillary at the top-center position. The SMF-capillary-SMF configuration excites an antiresonant (AR) guidance, and the balloon shape enhances the Mach-Zehnder interferometer (MZI). Experimental results show that, for a balloon length of 4.0 cm and a capillary length of 1.2 cm, the AR is insensitive to displacement and its sensitivity to temperature is 14.3 pm/°C, while the MZI has a sensitivity to displacement of 1.68 nm/mm in the range between 0 and 5 mm and a sensitivity to temperature of 28.6 pm/°C, twice the value of the AR. The proposed fiber sensor has only one sensing element in one configuration, which makes it simple to fabricate as well as low cost.

Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives.

BACKGROUND: Familial intestinal gastric cancer (FIGC) remains genetically unexplained and without testing/clinical criteria. Herein, we characterised the age of onset and disease spectrum of 50 FIGC families and searched for genetic causes potentially underlying a monogenic or an oligogenic/polygenic inheritance pattern. METHODS: Normal and tumour DNA from 50 FIGC probands were sequenced using Illumina custom panels on MiSeq, and their respective germline and somatic landscapes were compared with corresponding landscapes from sporadic intestinal gastric cancer (SIGC) and hereditary diffuse gastric cancer cohorts. RESULTS: The most prevalent phenotype in FIGC families was gastric cancer, detected in 138 of 208 patients (50 intestinal gastric cancer probands and 88 unknown gastric cancer histology relatives), followed by colorectal and breast cancers. After excluding benign and intronic variants lacking impact in splicing, 12 rare high-quality variants were found exclusively in 11 FIGC probands. Only two probands carried potentially deleterious variants, but lacked somatic second-hits, weakly supporting the monogenic hypothesis for FIGC. However, FIGC probands developed gastric cancer at least 10 years earlier and carried more TP53 germline common variants than SIGC (p=4.5E-03); FIGC and SIGC could be distinguished by specific germline and somatic variant profiles; there was an excess of FIGC tumours presenting microsatellite instability (38%); and FIGC tumours displayed significantly more somatic common variants than SIGC tumours (p=4.2E-06). CONCLUSION: This study proposed the first data-driven testing criteria for FIGC families, and supported FIGC as a genetically determined, likely polygenic, gastric cancer-predisposing disease, with earlier onset and distinct from patients with SIGC at the germline and somatic levels.

Optical Fiber Sensor for Monitoring the Evaporation of Ethanol-Water Mixtures.

An inline optical fiber sensor is proposed to monitor in real time the evaporation process of ethanol-water binary mixtures. The sensor presents two interferometers, a cladding modal interferometer (CMI) and a Mach-Zehnder interferometer (MZI). The CMI is used to acquire the variations in the external medium refractive index, presenting a maximum sensitivity of 387 nm/RIU, and to attain the variation in the sample concentration profile, while the MZI monitors temperature fluctuations. For comparison purposes, an image analysis is also conducted to obtain the droplet profile. The sensor proposed in this work is a promising alternative in applications where a rigorous measurement of volatile organic compound concentrations is required, and in the study of chemical and physical properties related to the evaporation process.

Real-Time Measurement of Refractive Index Using 3D-Printed Optofluidic Fiber Sensor.

This work describes a 3D-printed optofluidic fiber sensor to measure refractive index in real time, combining a microfluidic system with an optical fiber extrinsic Fabry-Perot interferometer. The microfluidic chip platform was developed for this purpose through 3D printing. The Fabry-Perot cavity was incorporated in the microfluidic chip perpendicularly to the sample flow, which was of approximately 3.7 µL/s. The optofluidic fiber sensor platform coupled with a low-cost optical power meter detector was characterized using different concentrations of glucose solutions. In the linear regression analysis, the optical power shift was correlated with the refractive index and a sensitivity of -86.6 dB/RIU (r2 = 0.996) was obtained. Good results were obtained in terms of stability with a maximum standard deviation of 0.03 dB and a sensor resolution of 5.2 × 10-4 RIU. The feasibility of the optofluidic fiber sensor for dynamic analyses of refractive index with low sample usage was confirmed through real-time measurements.

Binaural Acoustic Scene Classification Using Wavelet Scattering, Parallel Ensemble Classifiers and Nonlinear Fusion.

The analysis of ambient sounds can be very useful when developing sound base intelligent systems. Acoustic scene classification (ASC) is defined as identifying the area of a recorded sound or clip among some predefined scenes. ASC has huge potential to be used in urban sound event classification systems. This research presents a hybrid method that includes a novel mathematical fusion step which aims to tackle the challenges of ASC accuracy and adaptability of current state-of-the-art models. The proposed method uses a stereo signal, two ensemble classifiers (random subspace), and a novel mathematical fusion step. In the proposed method, a stable, invariant signal representation of the stereo signal is built using Wavelet Scattering Transform (WST). For each mono, i.e., left and right, channel, a different random subspace classifier is trained using WST. A novel mathematical formula for fusion step was developed, its parameters being found using a Genetic algorithm. The results on the DCASE 2017 dataset showed that the proposed method has higher classification accuracy (about 95%), pushing the boundaries of existing methods.

The Potential Roles of Extracellular Vesicles as Biomarkers for Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.

Sensitive skin: Active ingredients on the spotlight.

OBJECTIVE: Sensitive skin is characterized by self-reported sensory perceptions in response to stimuli that should not provoke unpleasant sensations. Cosmetic products for sensitive skin are designed to minimize these symptoms. This study aimed to unveil the most used active ingredients for sensitive skin in facial care products from the pharmacy and parapharmacy channel. METHODS: A pool of products from the pharmacy and parapharmacy channel whose label included the expressions 'sensitive skin', 'reactive skin' or 'intolerant skin' were analysed. The active ingredients were identified from product compositions and ranked in descending order of occurrence. The scientific evidence regarding the mechanism of action and efficacy of each ingredient was also compiled. RESULTS: Eighty-eight products from 19 multinational brands were included. Niacinamide leads the top, followed by Avena sativa, allantoin, glycyrrhetinic acid and derivatives and Laminaria ochroleuca. Ingredients that can reduce skin inflammation and act on the skin barrier were used in more than half of the products analysed. The clinical studies regarding the active ingredients used in these products remain sparse and lack methodological quality. Among the top ingredients, niacinamide, panthenol and acetyl dipeptide-1 cetyl ester were the only ones studied on volunteers having sensitive skin, while acetyl dipeptide-1 cetyl ester and palmitoyl tripeptide-8 were designed to act on the molecular targets involved in this condition. CONCLUSION: This study reveals the most used active ingredients in cosmetic products for sensitive skin, as well as the scientific evidence supporting their efficacy and the mechanisms of action. This insight is meaningful for dermatologists and other health professionals to provide customized advice based on the symptomatology of individuals with sensitive skin, and for the formulation of cosmetic products and design of new active ingredients.

OBJECTIF: La peau sensible se caractérise par des perceptions sensorielles autorapportées en réponse à des stimuli qui ne devraient pas provoquer de sensations désagréables. Les produits cosmétiques pour peaux sensibles sont conçus pour minimiser ces symptômes. Cette étude visait à dévoiler les principes actifs les plus utilisés pour les peaux sensibles dans les produits de soins du visage de la pharmacie et de la chaîne de parapharmacie. MÉTHODES: Un ensemble de produits de la chaîne pharmacie et parapharmacie, dont l'étiquette comportait les expressions « peau sensible ¼, « peau réactive ¼ ou « peau intolérante ¼ ont été analysés. Les principes actifs ont été identifiés à partir des compositions du produit et classés par ordre décroissant d'occurrence. Les preuves scientifiques concernant le mécanisme d'action et l'efficacité de chaque ingrédient ont également été compilées. RÉSULTATS: Quatre-vingt-huit produits provenant de 19 marques multinationales ont été inclus. Le niacinamide est en tête, suivi de l'Avena sativa, de l'allantoïne, de l'acide glycyrrhétinique et de ses dérivés et de Laminaria ochroleuca. Des ingrédients pouvant réduire l'inflammation cutanée et agir sur la barrière cutanée ont été utilisés dans plus de la moitié des produits analysés. Les études cliniques concernant les principes actifs utilisés dans ces produits restent rares et manquent de qualité méthodologique. Parmi les principaux ingrédients, le niacinamide, le panthénol et l'ester de dipeptide acétyl-1 ont été les seuls étudiés sur des volontaires ayant une peau sensible, tandis que l'ester de dipeptide acétyl-1 et le tripeptide palmitoyl-8 ont été conçus pour agir sur les cibles moléculaires qui interviennent dans cette affection. CONCLUSION: Cette étude révèle les principes actifs les plus utilisés dans les produits cosmétiques pour les peaux sensibles, ainsi que les preuves scientifiques étayant leur efficacité et les mécanismes d'action. Cet éclairage est important pour les dermatologues et autres professionnels de la santé pour apporter des conseils personnalisés basés sur la symptomatologie des personnes ayant la peau sensible, et pour la formulation de produits cosmétiques et la conception de nouveaux principes actifs.

Negative curvature hollow core fiber sensor for the measurement of strain and temperature.

Three different types of strain and temperature sensors based on negative curvature hollow core fiber (NCHCF) are proposed. Each sensor is produced by splicing a small section of the NCHCF between two sections of single mode fiber. Different types of interferometers are obtained simply by changing the splicing conditions. The first sensor consists on a single Fabry-Perot interferometer (FPI). The remaining two configurations are attained with the same sensing structure, depending on its position in relation to the interrogation setup. Thus, a double FPI or a hybrid sensor, the latter being composed by an FPI and a Michelson interferometer, are formed. The inline sensors are of submillimeter size, thus enabling nearly punctual measurements.

[18F]FDG PET radiomics to predict disease-free survival in cervical cancer: a multi-scanner/center study with external validation.

PURPOSE: To test the performances of native and tumour to liver ratio (TLR) radiomic features extracted from pre-treatment 2-[18F] fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT and combined with machine learning (ML) for predicting cancer recurrence in patients with locally advanced cervical cancer (LACC). METHODS: One hundred fifty-eight patients with LACC from multiple centers were retrospectively included in the study. Tumours were segmented using the Fuzzy Local Adaptive Bayesian (FLAB) algorithm. Radiomic features were extracted from the tumours and from regions drawn over the normal liver. Cox proportional hazard model was used to test statistical significance of clinical and radiomic features. Fivefold cross validation was used to tune the number of features. Seven different feature selection methods and four classifiers were tested. The models with the selected features were trained using bootstrapping and tested in data from each scanner independently. Reproducibility of radiomics features, clinical data added value and effect of ComBat-based harmonisation were evaluated across scanners. RESULTS: After a median follow-up of 23 months, 29% of the patients recurred. No individual radiomic or clinical features were significantly associated with cancer recurrence. The best model was obtained using 10 TLR features combined with clinical information. The area under the curve (AUC), F1-score, precision and recall were respectively 0.78 (0.67-0.88), 0.49 (0.25-0.67), 0.42 (0.25-0.60) and 0.63 (0.20-0.80). ComBat did not improve the predictive performance of the best models. Both the TLR and the native models performance varied across scanners used in the test set. CONCLUSION: [18F]FDG PET radiomic features combined with ML add relevant information to the standard clinical parameters in terms of LACC patient's outcome but remain subject to variability across PET/CT devices.

Convolutional neural networks for PET functional volume fully automatic segmentation: development and validation in a multi-center setting.

PURPOSE: In this work, we addressed fully automatic determination of tumor functional uptake from positron emission tomography (PET) images without relying on other image modalities or additional prior constraints, in the context of multicenter images with heterogeneous characteristics. METHODS: In cervical cancer, an additional challenge is the location of the tumor uptake near or even stuck to the bladder. PET datasets of 232 patients from five institutions were exploited. To avoid unreliable manual delineations, the ground truth was generated with a semi-automated approach: a volume containing the tumor and excluding the bladder was first manually determined, then a well-validated, semi-automated approach relying on the Fuzzy locally Adaptive Bayesian (FLAB) algorithm was applied to generate the ground truth. Our model built on the U-Net architecture incorporates residual blocks with concurrent spatial squeeze and excitation modules, as well as learnable non-linear downsampling and upsampling blocks. Experiments relied on cross-validation (four institutions for training and validation, and the fifth for testing). RESULTS: The model achieved good Dice similarity coefficient (DSC) with little variability across institutions (0.80 ± 0.03), with higher recall (0.90 ± 0.05) than precision (0.75 ± 0.05) and improved results over the standard U-Net (DSC 0.77 ± 0.05, recall 0.87 ± 0.02, precision 0.74 ± 0.08). Both vastly outperformed a fixed threshold at 40% of SUVmax (DSC 0.33 ± 0.15, recall 0.52 ± 0.17, precision 0.30 ± 0.16). In all cases, the model could determine the tumor uptake without including the bladder. Neither shape priors nor anatomical information was required to achieve efficient training. CONCLUSION: The proposed method could facilitate the deployment of a fully automated radiomics pipeline in such a challenging multicenter context.

Low-Field MRI of Stroke: Challenges and Opportunities.

Stroke is a leading cause of death and disability worldwide. The reasons for increased stroke burden in developing countries are inadequately controlled risk factors resulting from poor public awareness and inadequate infrastructure. Computed tomography and MRI are common neuroimaging modalities used to assess stroke with diffusion-weighted MRI, in particular, being the recommended choice for acute stroke imaging. However, access to these imaging modalities is primarily restricted to major cities and high-income groups. In the case of stroke, the time-window of treatment to limit the damage is of a few hours and needs a point-of-care diagnosis. A low-cost MR system typically achieved at the ultra-low- and very-low-field would meet the need for a geographically accessible and portable solution. We review studies focused on accessible stroke imaging and recent developments in MR methodologies, including hardware, to image at low fields. We hypothesize that in the absence of a formal, rapid stroke triaging system, the value of timely on-site delivery of the scanner to the stroke patient can be significant. To this end, we discuss multiple recent hardware and methods developments in the low-field regime. Our review suggests a compelling need to explore further the trade-offs between high signal, contrast, and accessibility at low fields in low-income communities. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 6.

Analysis of adolescent oncology cases from 2008 through 2018 in a tertiary-level hospital: an opportunity for improvement.

Purpose: The purpose of this study was to disclose the variability of pathways currently taken in the treatment of adolescent patients from diagnosis to final follow-up with a view to developing a more homogenous system. Patients & methods: A cross-sectional, observational and retrospective study of the cancer diagnosis and assignment to medical care teams in adolescent patients (12-20 years) from January 2008 to December 2018 was conducted. A total of 345 adolescent patients aged between 12 and 20 years, diagnosed with cancer and treated at Hospital Clinico Universitario Virgen de la Arrixaca were included. Results: CNS tumors, followed by leukemia were the most frequent tumors. At the time of diagnosis, the highest incidences of patients were assisted in the pediatrics service adult oncology service (21.7%) and hematology (11%). Conclusion: Our aim is to highlight the need for a better transition for patients from pediatric to adult oncology and hematology services.

Lay abstract This study shows the reality of the care of adolescent cancer patients in a hospital in southern Spain. A cross-sectional, observational and retrospective study of cancer diagnoses and assignment to medical care teams in adolescent patients (12­20 years) from January 2008 to December 2018 was conducted. A total of 345 adolescent patients between 12 and 20 years old who had a cancer diagnosis and were treated at Hospital Clinico Universitario Virgen de la Arrixaca were included. CNS tumors, followed by leukemia were the most frequent. At the time of diagnosis, the patients were most commonly attended by the pediatrics service, which concentrates 46.5% of the study population. There is great variability in the treatment and follow-up of the same tumors. The need for a better transition for patients from pediatric to adult oncology and hematology services is demonstrated.

Marine Ingredients for Sensitive Skin: Market Overview.

Marine ingredients are a source of new chemical entities with biological action, which is the reason why they have gained relevance in the cosmetic industry. The facial care category is the most relevant in this industry, and within it, the sensitive skin segment occupies a prominent position. This work analyzed the use of marine ingredients in 88 facial cosmetics for sensitive skin from multinational brands, as well as their composition and the scientific evidence that supports their efficacy. Marine ingredients were used in 27% of the cosmetic products for sensitive skin and included the species Laminaria ochroleuca, Ascophyllum nodosum (brown macroalgae), Asparagopsis armata (red macroalgae), and Chlorella vulgaris (microalgae). Carotenoids, polysaccharides, and lipids are the chemical classes highlighted in these preparations. Two ingredients, namely the Ascophyllum nodosum extract and Asparagopsis armata extracts, present clinical evidence supporting their use for sensitive skin. Overall, marine ingredients used in cosmetics for sensitive skin are proposed to reduce skin inflammation and improve the barrier function. Marine-derived preparations constitute promising active ingredients for sensitive skin cosmetic products. Their in-depth study, focusing on the extracted metabolites, randomized placebo-controlled studies including volunteers with sensitive skin, and the use of extraction methods that are more profitable may provide a great opportunity for the cosmetic industry.