The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

c.1103T>C (p.Ile368Th) de novo Variant in Synaptotagmin 1 (SYT1) Gene is Pathogenic, Leading to an Ultra-Rare Neurodevelopmental Disorder: The Baker-Gordon Syndrome.

Baker-Gordon Syndrome (BAGOS) is a genetically determined 4 (NDD), represented by a phenotypic spectrum of moderate to severe intellectual disability, resulting from mutations in the synaptotagmin 1 (SYT1) gene. Its prevalence is estimated at 1:1,000,000 and the known gene variants have indicated complete penetrance with variable expressivity. SYT1 is a membrane trafficking protein in presynaptic vesicles, which exerts a complex influence on synaptic transmission, with fundamental roles in the release of neurotransmitters and facilitators of endocytosis, impacting both neurotransmission and neuron plasticity. The current case report describes the first Brazilian male patient diagnosed at 17-year-old, and the 39th reported case globally using whole-exome sequencing. A de novo heterozygous missense mutation at chr12q:79448958 (NM_005639.2; c.1103T>C; p.Ile368Thr) in the SYT1 was found and classified as a pathogenic variant. The proband's clinical phenotype was compatible with BAGOS, involving behavioral changes such as irritability and severe intellectual disability. Knowledge about the mechanism of action and the extent of the genotypic and phenotypic presentations of the mutations in the SYT1 is still unfolding. Thus, we aimed to describe additional genotype-phenotype correlation for BAGOS, contributing to the expansion of the existing knowledge of such a heterogeneous ultra-rare syndrome, and, therefore, improve its diagnostic yield, case management, and therapeutic journey for future patients.

Biomedical image classification made easier thanks to transfer and semi-supervised learning.

BACKGROUND AND OBJECTIVES: Deep learning techniques are the state-of-the-art approach to solve image classification problems in biomedicine; however, they require the acquisition and annotation of a considerable volume of images. In addition, using deep learning libraries and tuning the hyperparameters of the networks trained with them might be challenging for several users. These drawbacks prevent the adoption of these techniques outside the machine-learning community. In this work, we present an Automated Machine Learning (AutoML) method to deal with these problems. METHODS: Our AutoML method combines transfer learning with a new semi-supervised learning procedure to train models when few annotated images are available. In order to facilitate the dissemination of our method, we have implemented it as an open-source tool called ATLASS. Finally, we have evaluated our method with two benchmarks of biomedical image classification datasets. RESULTS: Our method has been thoroughly tested both with small datasets and partially annotated biomedical datasets; and, it outperforms, both in terms of speed and accuracy, the existing AutoML tools when working with small datasets; and, might improve the accuracy of models up to a 10% when working with partially annotated datasets. CONCLUSIONS: The work presented in this paper allows the use of deep learning techniques to solve an image classification problem with few resources. Namely, it is possible to train deep models with small, and partially annotated datasets of images. In addition, we have proven that our AutoML method outperforms other AutoML tools both in terms of accuracy and speed when working with small datasets.

Prevalence of zoonotic intestinal parasites in domiciled dogs living in the urban area of Alfenas, State of Minas Gerais, Brazil.

Companion animals can carry pathogens that cause many infectious diseases in humans. In this sense, the present study aims to analyse the prevalence of zoonotic intestinal parasites in domiciled dogs living in the urban area of Alfenas, State of Minas Gerais, Brazil, from February 2017 to July 2018. To collect data, four regions of the city were considered as strata and their respective neighbourhoods as conglomerates, and one neighbourhood per stratum was selected. Stool samples were collected from 336 domiciled dogs and processed using the spontaneous sedimentation technique. The dog owners filled a questionnaire with information on the animals' living conditions. The parasites identified were Ancylostoma sp. and Toxocara canis, with higher prevalence of the former in male dogs, and of the latter in female dogs. Dogs of defined breed, small size, and age >1 year old exhibited the highest infection rates. To teach concepts of parasite transmission and prevention, the researchers developed educational actions with 6- to 10-year-old children who studied at schools from the selected neighbourhoods, as well as distributed informative folders to the dog owners. Laboratory tests confirmed the presence of potentially zoonotic intestinal parasites in 2.98% of the domiciled dogs living in Alfenas. Insufficient administration of deworming drugs (p=0.018) was the risk factor that significantly correlated with the occurrence of parasitic infection in the studied dog population. Educational actions favoured adoption of personal hygiene habits and good animal care practices to promote dog health and welfare and human health.

DeepClas4Bio: Connecting bioimaging tools with deep learning frameworks for image classification.

BACKGROUND AND OBJECTIVE: Deep learning techniques have been successfully applied to tackle several image classification problems in bioimaging. However, the models created from deep learning frameworks cannot be easily accessed from bioimaging tools such as ImageJ or Icy; this means that life scientists are not able to take advantage of the results obtained with those models from their usual tools. In this paper, we aim to facilitate the interoperability of bioimaging tools with deep learning frameworks. METHODS: In this project, called DeepClas4Bio, we have developed an extensible API that provides a common access point for classification models of several deep learning frameworks. In addition, this API might be employed to compare deep learning models, and to extend the functionality of bioimaging programs by creating plugins. RESULTS: Using the DeepClas4Bio API, we have developed a metagenerator to easily create ImageJ plugins. In addition, we have implemented a Java application that allows users to compare several deep learning models in a simple way using the DeepClas4Bio API. Moreover, we present three examples where we show how to work with different models and frameworks included in the DeepClas4Bio API using several bioimaging tools - namely, ImageJ, Icy and ImagePy. CONCLUSIONS: This project brings to the table benefits from several perspectives. Developers of deep learning models can disseminate those models using well-known tools widely employed by life-scientists. Developers of bioimaging programs can easily create plugins that use models from deep learning frameworks. Finally, users of bioimaging tools have access to powerful tools in a known environment for them.

SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018)

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided

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SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018).

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

Subacute intoxication with sodium nitrate induces hematological and biochemical alterations and liver injury in male Wistar rats.

Nitrate pollution has emerged as a problem of great importance because in recent years, the levels of nitrate in soil and groundwater have increased, mainly through anthropogenic activities, such as the use of fertilizers in agriculture, domestic wastewater and septic tanks, industrial waste and deforestation. In animals, nitrate reduction to nitrite (NO2) and nitric oxide (NO) promote the formation of methemoglobin in the blood and the generation of highly reactive intermediates that induce oxidative stress in target organs. Exposition to nitrates has been associated with methemoglobinemia, reproductive toxicity, metabolic and endocrine alterations and cancer. This study analyzed acute intoxication with sodium nitrate (NaNO3) in male Wistar rats, aged 12-16 weeks. Four groups with n = 10 rats each were formed: group 1 was the control, and group 2, group 3 and group 4 were treated for 10 days with intragastric doses of 19, 66 and 150 mg/kg/d NaNO3, respectively. Hematological, metabolic and histological biomarkers in the liver were analyzed. The results showed high percentages of methemoglobin, an increase in NO2 in the plasma and an accumulation in the liver. Moreover, there were high counts of white blood cells and platelets in all treated groups. Additionally, there was an increase in the spleen weight in group 4. High levels of glucose, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed and were significantly increased in groups 3 and 4. For oxidative stress biomarkers, there were increases in Thiobarbituric Acid Reactive Substances (TBARS), total GSH and SOD activity, mainly in group 4. Changes in mitochondrial activity were not significant. Histopathological analyses of the liver showed inflammation, infiltration of mononuclear cells, steatosis, ischemia and necrosis, and these findings were more evident at high doses of NaNO3 in which high of S-nitrosylation were found. In conclusion, NaNO3 was reduced to NO2, thereby inducing methemoglobinemia, whereas other reactive species generated oxidative stress, causing hematological and metabolic alterations and injury to the liver.

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Bacterial Community Dynamics across the Gastrointestinal Tracts of Dairy Calves during Preweaning Development.

Microbial communities play critical roles in the gastrointestinal tracts (GIT) of preruminant calves by influencing performance and health. However, little is known about the establishment of microbial communities in the calf GIT or their dynamics during development. In this study, next-generation sequencing was used to assess changes in the bacterial communities of the rumen, jejunum, cecum, and colon in 26 crossbred calves at four developmental stages (7, 28, 49, and 63 days old). Alpha diversity differed among GIT regions with the lowest diversity and evenness in the jejunum, whereas no changes in alpha diversity were observed across developmental stage. Beta diversity analysis showed both region and age effects, with low numbers of operational taxonomic units (OTUs) shared between regions within a given age group or between ages in a given region. Taxonomic analysis revealed that several taxa coexisted in the rumen, jejunum, cecum, and colon but that their abundances differed considerably by GIT region and age. As calves aged, we observed lower abundances of taxa such as Bacteroides, Parabacteroides, and Paraprevotella with higher abundances of Bulleidia and Succiniclasticum in the rumen. The jejunum also displayed taxonomic changes with increases in Clostridiaceae and Turicibacter taxa in older calves. In the lower gut, taxa such as Lactobacillus, Blautia, and Faecalibacterium decreased and S24-7, Paraprevotella, and Prevotella increased as calves aged. These data support a model whereby early and successive colonization by bacteria occurs across the GIT of calves and provides insights into the temporal dynamics of the GIT microbiota of dairy calves during preweaning development.IMPORTANCE The gastrointestinal tracts (GIT) of ruminants, such as dairy cows, house complex microbial communities that contribute to their overall health and support their ability to produce milk. For example, the rumen microbiota converts feed into usable nutrients, while the jejunal microbiota provides access to protein. Thus, establishing a properly functioning GIT microbiota in dairy calves is critical to their productivity as adult cows. However, little is known about the establishment, maintenance, and dynamics of the calf GIT microbiota in early life. In this study, we evaluated the bacterial communities in the rumen, jejunum, cecum, and colon in dairy calves across preweaning development and show that they are highly variable early on in life before transitioning to a stable community. Understanding the dairy calf GIT microbiota has implications for ensuring proper health during early life and will aid in efforts to develop strategies for improving downstream production.

Antibiogramj: A tool for analysing images from disk diffusion tests.

BACKGROUND AND OBJECTIVES: Disk diffusion testing, known as antibiogram, is widely applied in microbiology to determine the antimicrobial susceptibility of microorganisms. The measurement of the diameter of the zone of growth inhibition of microorganisms around the antimicrobial disks in the antibiogram is frequently performed manually by specialists using a ruler. This is a time-consuming and error-prone task that might be simplified using automated or semi-automated inhibition zone readers. However, most readers are usually expensive instruments with embedded software that require significant changes in laboratory design and workflow. METHODS: Based on the workflow employed by specialists to determine the antimicrobial susceptibility of microorganisms, we have designed a software tool that, from images of disk diffusion tests, semi-automatises the process. Standard computer vision techniques are employed to achieve such an automatisation. RESULTS: We present AntibiogramJ, a user-friendly and open-source software tool to semi-automatically determine, measure and categorise inhibition zones of images from disk diffusion tests. AntibiogramJ is implemented in Java and deals with images captured with any device that incorporates a camera, including digital cameras and mobile phones. The fully automatic procedure of AntibiogramJ for measuring inhibition zones achieves an overall agreement of 87% with an expert microbiologist; moreover, AntibiogramJ includes features to easily detect when the automatic reading is not correct and fix it manually to obtain the correct result. CONCLUSIONS: AntibiogramJ is a user-friendly, platform-independent, open-source, and free tool that, up to the best of our knowledge, is the most complete software tool for antibiogram analysis without requiring any investment in new equipment or changes in the laboratory.

[Results of the Salters osteotomy as a definitive treatment for the developmental dysplasia of the hip]. / Resultados de la osteotomía tipo Salter como tratamiento definitivo en displasia del desarrollo de la cadera.

OBJECTIVE: Evaluate the results of open reduction associated to a Salter osteotomy at nine months of age for treatment of the developmental Dysplasia of the Hip. MATERIAL AND METHODS: Case- series of unilateral Developmental Dysplasia of the hip treated between July 2004- December 2008 with follow-up at 3, 6 and 9 months postop. RESULTS: 16 patients, 13 females (81%) 3 males (19%). we did an open reduction and Salters osteotomy at 9 months on average (8- 10 months); the most effected side were the left hip on 75%. at 9 months of follow up 15 patients had a McKay score excellent and 1 good. Only one patient was followed up at one year with no pain, full range of motion and stable. CONCLUSION: open reduction and salter osteotomy without preoperative traction is an effective treatment in the short-term; the range of motion could be affected. It is important that the spica cast were applied in a staged manner and in secured position.

OBJETIVO: Evaluar los resultados de la reducción abierta asociada a una osteotomía tipo Salter a los nueve meses de edad como tratamiento en la displasia del desarrollo de la cadera. MATERIAL Y MÉTODOS: Serie de casos con pacientes con diagnóstico de displasia del desarrollo de cadera unilateral en un período comprendido de Julio de 2004 a Diciembre de 2008 y seguimiento a los tres, seis y nueve meses del postquirúrgico. RESULTADOS: 16 pacientes, 13 del sexo femenino (81%) y tres del sexo masculino (19%). Se les realizó reducción abierta con osteotomía tipo Salter a los nueve meses de edad (de ocho a 10 meses) en promedio. El lado afectado más frecuente fue en cadera izquierda en 75% y cadera derecha en 25%. A los nueve meses de evolución 15 pacientes presentaron un puntaje de McKay excelente y sólo un paciente mostró McKay bueno. Sólo un paciente fue valorado al año de la última cirugía con cadera estable, sin dolor y disminución del rango de movilidad tanto en flexión y abducción en relación con la cadera contralateral. CONCLUSIÓN: La reducción abierta con una osteotomía de tipo Salter sin una tracción preoperatoria es un tratamiento efectivo en el corto plazo. Puede haber restricciones en la movilidad. Es importante el uso del aparato de yeso en forma pausada y en una posición de reducción segura.