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El estudio se enfoca en el desarrollo de un micro generador hidroeléctrico mediante el empleo de una turbina de flujo cruzado de admisión inferior que aprovecha el potencial hidráulico de los canales de riego. La metodología utilizada es cuantitativa y experimental, y se basa en un diagrama de flujo que describe las etapas desde la creación hasta la implementación del prototipo. Se tomaron en cuenta variables como la altura y el caudal del agua, así como las dimensiones del canal de riego, las cuales no podían modificarse debido a las actividades agrícolas que se llevan a cabo en el lugar. Los resultados obtenidos de la implementación en campo del prototipo diseñado demuestran que el generador tiene la capacidad de alcanzar un valor de potencia de 93 W con un porcentaje de eficiencia del 11.3% el mismo que produce energía de manera sostenible en áreas remotas. En conclusión, el estudio resalta la necesidad de explorar nuevas fuentes de energía renovales y sostenibles en respuesta a la crisis energética actual que afecta a la sociedad; se enfatiza la imprescindibilidad por adoptar alternativas energéticas más limpias que limite la dependencia por los recursos no renovables a la par de controlar los efectos negativos del cambio climático.

As phenomics data volume and dimensionality increase due to advancements in sensor technology, there is an urgent need to develop and implement scalable data processing pipelines. Current phenomics data processing pipelines lack modularity, extensibility, and processing distribution across sensor modalities and phenotyping platforms. To address these challenges, we developed PhytoOracle (PO), a suite of modular, scalable pipelines for processing large volumes of field phenomics RGB, thermal, PSII chlorophyll fluorescence 2D images, and 3D point clouds. PhytoOracle aims to (i) improve data processing efficiency; (ii) provide an extensible, reproducible computing framework; and (iii) enable data fusion of multi-modal phenomics data. PhytoOracle integrates open-source distributed computing frameworks for parallel processing on high-performance computing, cloud, and local computing environments. Each pipeline component is available as a standalone container, providing transferability, extensibility, and reproducibility. The PO pipeline extracts and associates individual plant traits across sensor modalities and collection time points, representing a unique multi-system approach to addressing the genotype-phenotype gap. To date, PO supports lettuce and sorghum phenotypic trait extraction, with a goal of widening the range of supported species in the future. At the maximum number of cores tested in this study (1,024 cores), PO processing times were: 235 minutes for 9,270 RGB images (140.7 GB), 235 minutes for 9,270 thermal images (5.4 GB), and 13 minutes for 39,678 PSII images (86.2 GB). These processing times represent end-to-end processing, from raw data to fully processed numerical phenotypic trait data. Repeatability values of 0.39-0.95 (bounding area), 0.81-0.95 (axis-aligned bounding volume), 0.79-0.94 (oriented bounding volume), 0.83-0.95 (plant height), and 0.81-0.95 (number of points) were observed in Field Scanalyzer data. We also show the ability of PO to process drone data with a repeatability of 0.55-0.95 (bounding area).

La Universidad Nacional y, particularmente, la escuela de posgrado, tienen la tarea de brindar un servicio de calidad que genere satisfacción entre sus estudiantes. Esto es fundamental para mejorar la calidad de los programas de posgrado. La investigación tuvo como objetivo establecer la relación que existen entre la calidad del servicio universitario ofrecido con la satisfacción del usuario en estudiantes de posgrado de una Universidad Pública de Lima. Para lograrlo se utilizó un diseño no experimental, correlacional y transversal con una muestra de 180 estudiantes, a quienes se les administró el cuestionario sobre calidad del servicio universitario y el cuestionario sobre satisfacción del usuario. Los resultados obtenidos permitieron concluir que, existen relaciones significativas entre las dos variables de estudio (r = 0.80), así como entre sus dimensiones que componen cada variable.

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations.

Abstract Background Psoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention. Objective To characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis). Method Cross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated. Results The groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p < 0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho = 0.39; p = 0.02), and lower dietary fiber intake (rho = −0.71; p < 0.01). Study limitations Only adult men were evaluated. Conclusion A difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.

Background: Erythrocytosis is a relatively common condition, however a large proportion of these patients (70%) remain without a clear etiologic explanation. Methods: We set up a targeted NGS panel for patients with erythrocytosis and 118 sporadic patients with idiopathic erythrocytosis were studied. Results: In 40 (34%) patients no variant was found while in 78 (66%) we identified at least one germinal variant; 55 patients (70.5%) had 1 altered gene, 18 (23%) had 2 alterations, and 5 (6.4%) had 3. An altered HFE gene was observed in 51 cases (57.1%), EGLN1 in 18 (22.6%) and EPAS1, EPOR, JAK2, and TFR2 variants in 7.7%, 10.3%, 11.5%, and 14.1% patients, respectively. In 23 patients (19.45%), more than 1 putative variant was found in multiple genes. Conclusions: Genetic variants in patients with erythrocytosis were detected in about 2/3 of our cohort. A NGS panel including more candidate genes should reduce the number of cases diagnosed as “idiopathic” erythrocytosis in whom a cause cannot yet be identified. It is known that HFE variants are common in idiopathic erythrocytosis. TFR2 alterations supports the existence of a relationship between genes involved in iron metabolism and impaired erythropoiesis. Some novel multiple variants were identified. Erythrocytosis appears to be often of multigenic nature.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

Abstract Background Leigh Syndrome (LS) is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors. Case presentation Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB) and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA. Conclusions The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.

Abstract ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines. Their expression has been validated using several unbiased techniques, including Nanopore sequencing. Most of these transcripts originate from an in-frame exon skipping and, thus, are expected to be translated into ETV4 protein isoforms. Functional analysis of the most abundant among these isoforms shows that they still bear an activity, namely a reduced ability to promote proliferation and a residual ability to regulate the transcription of ETV4 target genes. Alternatively spliced genes are common in cancer cells: an analysis of the TCGA dataset confirms the abundance of these novel ETV4 transcripts in prostate tumors, in contrast to peritumoral tissues. Since none of their translated isoforms have acquired a higher oncogenic potential, such abundance is likely to reflect the tumor deranged splicing machinery. However, it is also possible that their interaction with the canonical variants may contribute to the biology and the clinics of prostate cancer. Further investigations are needed to elucidate the biological role of these ETV4 transcripts and of their putative isoforms.

El propósito del trabajo de investigación fue establecer los niveles de adicción a las redes sociales en estudiantes de una universidad privada de Lima durante el año 2021. Se realizó un estudio descriptivo correlacional, donde la muestra fue probabilística y estuvo representada por 360 estudiantes de una universidad privada de Lima, a quienes se les aplicó el cuestionario de Adicción a Redes Sociales de Salas y Escurra (ARS). Los resultados indican que la falta de control personal en el uso de redes sociales está relacionado significativamente con los estudiantes universitarios de 16 a 26 años. Asimismo, los resultados estadísticos descriptivos nos informan que la adición de redes sociales que presentan los estudiantes de la muestra se ubica en un nivel medio que representa un 58,3 % de la muestra seleccionada.

IntroductionThe placenta is essential for fetal growth and survival and maintaining a successful pregnancy. The sterility of the placenta has been challenged recently; however, the presence of a placental microbiome has been controversial. We tested the hypothesis that the bacterial extracellular vesicles (BEVs) from Gram-negative bacteria as an alternate source of microbial DNA, regardless of the existence of a microbial community in the placenta.MethodsPlacentae from the term, not in labor Cesareans deliveries, were used for this study, and placental specimens were sampled randomly from the fetal side. We developed a protocol for the isolation of BEVs from human tissues and this is the first study to isolate the BEVs from human tissue and characterize them.ResultsThe median size of BEVs was 130–140 nm, and the mean concentration was 1.8–5.5 × 1010 BEVs/g of the wet placenta. BEVs are spherical and contain LPS and ompA. Western blots further confirmed ompA but not human EVs markers ALIX confirming the purity of preparations. Taxonomic abundance profiles showed BEV sequence reads above the levels of the negative controls (all reagent controls). In contrast, the sequence reads in the same placenta were substantially low, indicating nothing beyond contamination (low biomass). Alpha-diversity showed the number of detected genera was significantly higher in the BEVs than placenta, suggesting BEVs as a likely source of microbial DNA. Beta-diversity further showed significant overlap in the microbiome between BEV and the placenta, confirming that BEVs in the placenta are likely a source of microbial DNA in the placenta. Uptake studies localized BEVs in maternal (decidual) and placental cells (cytotrophoblast), confirming their ability to enter these cells. Lastly, BEVs significantly increased inflammatory cytokine production in THP-1 macrophages in a high-dose group but not in the placental or decidual cells.ConclusionWe conclude that the BEVs are normal constituents during pregnancy and likely reach the placenta through hematogenous spread from maternal body sites that harbor microbiome. Their presence may result in a low-grade localized inflammation to prime an antigen response in the placenta; however, insufficient to cause a fetal inflammatory response and adverse pregnancy events. This study suggests that BEVs can confound placental microbiome studies, but their low biomass in the placenta is unlikely to have any immunologic impact.

The atmospheric response for MeV γ rays (∼0.1–10 MeV) can be characterized in terms of two observed components. The first component is due to photons that reach the detector without scattering. The second component is due to photons that reach the detector after scattering one or more times. While the former can be determined in a straightforward manner, the latter is much more complex to quantify, as it requires tracking the transport of all source photons that are incident on Earth’s atmosphere. The scattered component can cause a significant energy-dependent distortion in the measured spectrum, which is important to account for when making balloon-borne observations. In this work, we simulate the full response for γ -ray transport in the atmosphere. We find that the scattered component becomes increasingly more significant toward lower energies, and at 0.1 MeV, it may increase the measured flux by as much as a factor of ∼2–4, depending on the photon index and off-axis angle of the source. This is particularly important for diffuse sources, whereas the effect from scattering can be significantly reduced for point sources observed with an imaging telescope.

Intrauterine growth restriction (IUGR) enhances risk for adult onset cardiovascular disease (CVD). The mechanisms underlying IUGR are poorly understood, though inadequate blood flow and oxygen/nutrient provision are considered common endpoints. Based on evidence in humans linking IUGR to adult CVD, we hypothesized that in murine pregnancy, maternal late gestational hypoxia (LG-H) exposure resulting in IUGR would result in (1) placental transcriptome changes linked to risk for later CVD, and 2) adult phenotypes of CVD in the IUGR offspring. After subjecting pregnant mice to hypoxia (10.5% oxygen) from gestational day (GD) 14.5 to 18.5, we undertook RNA sequencing from GD19 placentas. Functional analysis suggested multiple changes in structural and functional genes important for placental health and function, with maximal dysregulation involving vascular and nutrient transport pathways. Concordantly, a ~10% decrease in birthweights and ~30% decrease in litter size was observed, supportive of placental insufficiency. We also found that the LG-H IUGR offspring exhibit increased risk for CVD at 4 months of age, manifesting as hypertension, increased abdominal fat, elevated leptin and total cholesterol concentrations. In summary, this animal model of IUGR links the placental transcriptional response to the stressor of gestational hypoxia to increased risk of developing cardiometabolic disease.

Introduction The purpose of the research project is to analyze the long-term evolution of obsessive-compulsive disorder (OCD) from of a study of a cohort of patients prospectively followed over a period ranging from 5 to 20 years, treated for according to therapeutic guidelines mediating serotonin reuptake inhibitors (IRS) and drug enhancers (antipsychotics) and cognitive behavioral therapy and evaluated in a standardized manner. Objectives To assess the long-term course of Obsessive-Compulsive Disorder (OCD) in a cohort of patients treated according to current clinical guidelines; to analyse possible prognostic factors associated with the long-term course of the disorder including clinical and sociodemographic variables, as well as genetic and neuroimaging biomarkers, and their interaction, and finally to study neuroanatomical and functional cerebral connectivity changes after 15 years of treatment in a subsample of patients. Methods Prospective, descriptive, and observational study of a cohort of OCD patients, receiving treatment at the Department of Psychiatry of Hospital de Bellvitge since 1998, according to a standardized protocol. Follow-up period ranges from 5 (n=423), to 10 (n= 247) and 15 years (123). Baseline clinical and sociodemographic assessment, long-term evolution and information on treatments provided are available for the whole sample. Data on whole exome sequencing is available for 300 of the patients included in the cohort and baseline structural neuroimaging and cerebral functional connectivity has been analysed in 168 subjects. To expand the analysis of genetic biomarkers, we propose the study of de novo variants through exome analysis of 50 trios (patient and both parents) selected among those subjects that have reached 15 years of follow-up (25 trios with patients within the “long-term remission” group and 25 trios with patients with chronic OCD). De novo variants detected in the trio analysis will be replicated in the rest of the sample. A structural and resting state MRI will be obtained in a subsample of 100 patients recruited among those who have completed a minimum follow-up period of 15 years, to assess cerebral changes associated with the long-term course of the disorder. Results in the current moment the recruitment period of the study has ended and all the data is being statistically analysed in order to provide solid results in a short period of time. Conclusions The identification of those factors associated with an increased risk of chronic disease is an element essential to offer personalized treatment to our patients and improve their prognosis, emphasizing the intensive use of those therapeutic strategies for which we can predict a better response and modifying to the extent of, if possible, environmental factors or factors of access to treatment that contribute to perpetuate obsessive symptoms. Disclosure of Interest None Declared

As phenomics data volume and dimensionality increase due to advancements in sensor technology, there is an urgent need to develop and implement scalable data processing pipelines. Current phenomics data processing pipelines lack modularity, extensibility, and processing distribution across sensor modalities and phenotyping platforms. To address these challenges, we developed PhytoOracle (PO), a suite of modular, scalable pipelines for processing large volumes of field phenomics RGB, thermal, PSII chlorophyll fluorescence 2D images, and 3D point clouds. PhytoOracle aims to (i) improve data processing efficiency; (ii) provide an extensible, reproducible computing framework; and (iii) enable data fusion of multi-modal phenomics data. PhytoOracle integrates open-source distributed computing frameworks for parallel processing on high-performance computing, cloud, and local computing environments. Each pipeline component is available as a standalone container, providing transferability, extensibility, and reproducibility. The PO pipeline extracts and associates individual plant traits across sensor modalities and collection time points, representing a unique multi-system approach to addressing the genotype-phenotype gap. To date, PO supports lettuce and sorghum phenotypic trait extraction, with a goal of widening the range of supported species in the future. At the maximum number of cores tested in this study (1,024 cores), PO processing times were: 235 minutes for 9,270 RGB images (140.7 GB), 235 minutes for 9,270 thermal images (5.4 GB), and 13 minutes for 39,678 PSII images (86.2 GB). These processing times represent end-to-end processing, from raw data to fully processed numerical phenotypic trait data. Repeatability values of 0.39-0.95 (bounding area), 0.81-0.95 (axis-aligned bounding volume), 0.79-0.94 (oriented bounding volume), 0.83-0.95 (plant height), and 0.81-0.95 (number of points) were observed in Field Scanalyzer data. We also show the ability of PO to process drone data with a repeatability of 0.55-0.95 (bounding area).

This article discusses a novel type of allergy syndrome caused by allergic reactions to horse chestnut seeds. The reactions are triggered by sensitization to mugwort pollen, and the study identified a defensin protein called Aes h 1 as the allergen responsible. The protein shares similarities with Art v 1, a major allergen in mugwort pollen. The findings highlight the potential for cross-reactivity between different defensins and raise awareness among clinicians and patients about the risk of allergic reactions to horse chestnut seeds. [Extracted from the article]

The development of emotional competencies has become a priority in the educational field at all levels, as it allows improving the aspirational level of university students, in addition to allowing an efficient development of their learning strategies. From this point of view, the main objective of this research was to determine the connection between emotional competencies and self-regulated learning in a sample of general studies students at Norbert Wiener University. A non-experimental correlational design was achieved, with a sample of 344 subjects, to whom two questionnaires were applied to evaluate each of the variables. These instruments were evaluated and the statistical results showed consistent levels of validity and reliability. The data that was produced was processed statistically and it was limited that the variables were found to be significantly linked (r = 0.67 p < .001), so the first research hypothesis was accepted. The specific analyzes show that the areas of both variables are also significantly linked, which is why it is concluded that all the specific hypotheses that were formulated are accepted in the present investigation.

Over the last decade, the therapeutic scenario for advanced non-small-cell lung cancer (NSCLC) has undergone a major paradigm shift. Immune checkpoint inhibitors (ICIs) have shown a meaningful clinical and survival improvement in different settings of the disease. However, the real benefit of this therapeutic approach remains controversial in selected NSCLC subsets, such as those of the elderly with active brain metastases or oncogene-addicted mutations. This is mainly due to the exclusion or underrepresentation of these patient subpopulations in most pivotal phase III studies; this precludes the generalization of ICI efficacy in this context. Moreover, no predictive biomarkers of ICI response exist that can help with patient selection for this therapeutic approach. Here, we critically summarize the current state of ICI efficacy in the most common “special” NSCLC subpopulations.

The aim of this study was to determine the presence of beta-lactamase- (bla) producing Enterobacteriaceae in hospital effluent samples from two level II and III hospitals in Lima, Peru. The resistance profile of the isolated bacteria was identified and characterized using the MicroScan system for 18 antimicrobials, and the presence of extended spectrum beta-lactamases (ESBL) (blaCTX-M, blaSHV blaTEM, blaPER) and carbapenemases (blaKPC, blaNDM, blaVIM, blaIMP) resistance genes was determined by conventional PCR. Thirty-two isolates were identified (20 Enterobacteriaceae and 12 gram-negative bacteria). All the isolated bacteria showed multidrug resistance. ESBL (blaTEM) and carbapenemase (blaKPC, blaIMP) genes were found in samples from the hospitals that we evaluated. The release of these microorganisms to public areas and the lack of treatment of the hospital effluents could be an important public health problem.

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations. [ABSTRACT FROM AUTHOR]

Background. The term "incel" (involuntary celibate) refers to the members of an online subculture, mainly composed of heterosexual men. These individuals find it difficult or impossible to have a romantic and/or sexual partner, and they express extreme anger and resentment toward women, as they hold them accountable for their "inceldom." In recent years, online and offline acts of violence have been perpetrated by incels, raising concern at social and political levels. This study aims to understand the personal, psychological, and psychopathological variables that may contribute to developing incel traits. Materials and Methods. A total of 800 Italian heterosexual cisgender men were recruited by a link to the survey forwarded on social networks. Participants have completed a sociodemographic questionnaire and a set of psychometric tests to assess incels' personality traits, attachment patterns, paranoia, anxiety, and depression. Results. Positive correlations among incel personality traits and psychopathological symptoms and insecure attachment were found. Hierarchical regression analysis showed the significant role of paranoid thinking, insecure attachment, depression, and anxiety symptoms in the presence of incels' personality traits. Conclusion. Therefore, the assessment of these psychopathological aspects could help clinicians, parents, and teachers to early identify young males that can be caught in the inceldom and to develop specific intervention programs to prevent violence. [ABSTRACT FROM AUTHOR]

Very rare, peculiar congenital bleeding disorders are usually dealt with in clinics without giving much importance. We think that this practice is not correct since the disorders may often provide useful information about blood coagulation. In this review, we assess very rare bleeding conditions. We refer to the defects of the fibrinolytic system, alpha 1-antitrypsin Pittsburg, few dysprothrombinemias, east Texas or short FV defect, FIX Padua, and thrombomodulin (TM) abnormality. These defects are usually not included in rare bleeding disorders. Patients were gathered from two sources: personal files and two time-unlimited PubMed searches carried out on February 2010 and July 2019. Combined defects were disregarded. These rare bleeding conditions are often unrecognized even though some of them, such as antiplasmin deficiency, are not that rare with more than 30 cases reported already. The underevaluation of the fibrinolytic defects is due to the decrease in the use of methods capable of detecting increased fibrinolysis in routine laboratory study. The limited use of immunological tests represents a second drawback as in the dysprothrombinemia, east Texas Factor V, and FIX Padua. Finally, the limited use of assays of natural inhibitors such as tissue factor pathway inhibitor and TM has played a role in delaying east Texas FX recognition and TM defect. The study of rare, peculiar bleeding disorders has been very important in clarifying the nature of the defects, and it has even allowed the identification of mutations that may turn them from prohemorrhagic to prothrombotic in some of these proteins. This has greatly contributed to the understanding of the complex relationship existing among clotting defects. [JBCGenetics 2020; 3(2.000): 84-93]