Reference interval of free light chains ratio in patients with end-stage renal disease on chronic hemodialysis.

Not available.

Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis).

BACKGROUND: Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. RESULTS: Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. CONCLUSIONS: We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon.

Dominance of ST131, B2, blaCTX-M-15, and papA-papC-kpsMII-uitA among ESBL Escherichia coli isolated from bloodstream infections in Quito, Ecuador: a 10-year surveillance study (2009-2019).

AIMS: This study aimed to examine antibiotic resistance and the epidemiology of extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli associated with bloodstream infections over a period of 10 years. METHODS AND RESULTS: Isolates were collected from January 2009 to December 2019 and those testing for E. coli were included. Antibiotic susceptibility was tested using the VITEK® system. Selected isolates were further characterized by amplification of marker genes (virulence traits, phylogroups, and sequence types). A total of 166 ESBL-producing E. coli were recovered. The blaCTX-M-15 allele was the most abundant. Most of the isolates were resistant to ceftriaxone, cefepime, ceftazidime, ampicillin/sulbactam, piperacillin/tazobactam, and ciprofloxacin. No resistance to carbapenems was registered. More than 80% of bacteria were classified as extraintestinal pathogenic E. coli (ExPEC), and the combination of virulence traits:papA-papC-kpsMII-uitA was the most common. Phylogroup B2 was the most prevalent, and bacteria predominantly belonged to ST131. CONCLUSIONS: There was an increase in the ExPEC ESBL-E coli in bloodstream infections and the relationship between the isolates found in these infections during these 10 years.

A Survey of AI-Based Anomaly Detection in IoT and Sensor Networks.

Machine learning (ML) and deep learning (DL), in particular, are common tools for anomaly detection (AD). With the rapid increase in the number of Internet-connected devices, the growing desire for Internet of Things (IoT) devices in the home, on our person, and in our vehicles, and the transition to smart infrastructure and the Industrial IoT (IIoT), anomaly detection in these devices is critical. This paper is a survey of anomaly detection in sensor networks/the IoT. This paper defines what an anomaly is and surveys multiple sources based on those definitions. The goal of this survey was to highlight how anomaly detection is being performed on the Internet of Things and sensor networks, identify anomaly detection approaches, and outlines gaps in the research in this domain.

An elevated HScore is associated with poor clinical outcomes in COVID-19.

BACKGROUND: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome leading to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. A scoring system (HScore) that evaluates underlying immunosuppression, temperature, organomegaly, cytopenias, ferritin, triglycerides, fibrinogen and AST was validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. AIM: To assess the presence of sHLH among patients with COVID-19 admitted for hospitalization and to evaluate Hscore as a prognostic tool for poor outcomes. MATERIAL AND METHODS: One hundred forty-three patients aged 21-100 years (64% males) admitted because of COVID-19 were enrolled in a prospective study. HScore was calculated within 72 hours admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between a HScore ≥ 130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. RESULTS: The median HScore was 96 (33-169). A SHLH was diagnosed in one patient (incidence 0.7%), whose HScore was 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥ 130 was independently associated with the composite clinical outcome (Hazard rartio 2.13, p = 0.022). CONCLUSIONS: sHLH is not frequent among COVID-19 patients. HScore can be useful to predict the risk for poor outcomes.

Preventing Postendoscopic Mucosal Resection Bleeding of Large Nonpedunculated Colorectal Lesions.

The most common major adverse event of endoscopic mucosal resection (EMR) is clinically significant post-EMR bleeding (CSPEB), with an incidence of 6%-7% in large lesions. Repeat colonoscopy, blood transfusions, or other interventions are often needed. The associated direct costs are much higher than those of an uncomplicated EMR. In this review, we discuss the aspects related to CSPEB of large nonpedunculated polyps, such as risk factors, predictive models, and prophylactic measures, and we highlight evidence for preventive treatment options and explore new methods for bleeding prophylaxis. We also provide recommendations for steps that can be taken before, during, and after EMR to minimize bleeding risk. Finally, this review proposes future directions to reduce CSPEB incidence.

Prophylactic Clipping After Colorectal Endoscopic Resection Prevents Bleeding of Large, Proximal Polyps: Meta-analysis of Randomized Trials.

BACKGROUND & AIMS: The benefits of prophylactic clipping to prevent bleeding after polypectomy are unclear. We conducted an updated meta-analysis of randomized trials to assess the efficacy of clipping in preventing bleeding after polypectomy, overall and according to polyp size and location. METHODS: We searched the MEDLINE/PubMed, Embase, and Scopus databases for randomized trials that compared the effects of clipping vs not clipping to prevent bleeding after polypectomy. We performed a random-effects meta-analysis to generate pooled relative risks (RRs) with 95% CIs. Multilevel random-effects metaregression analysis was used to combine data on bleeding after polypectomy and estimate associations between rates of bleeding and polyp characteristics. RESULTS: We analyzed data from 9 trials, comprising 71897 colorectal lesions (22.5% 20 mm or larger; 49.2% with proximal location). Clipping, compared with no clipping, did not significantly reduce the overall risk of postpolypectomy bleeding (2.2% with clipping vs 3.3% with no clipping; RR, 0.69; 95% confidence interval [CI], 0.45-1.08; P = .072). Clipping significantly reduced risk of bleeding after removal of polyps that were 20 mm or larger (4.3% had bleeding after clipping vs 7.6% had bleeding with no clipping; RR, 0.51; 95% CI, 0.33-0.78; P = .020) or that were in a proximal location (3.0% had bleeding after clipping vs 6.2% had bleeding with no clipping; RR, 0.53; 95% CI, 0.35-0.81; P < .001). In multilevel metaregression analysis that adjusted for polyp size and location, prophylactic clipping was significantly associated with reduced risk of bleeding after removal of large proximal polyps (RR, 0.37; 95% CI, 0.22-0.61; P = .021) but not small proximal lesions (RR, 0.88; 95% CI, 0.48-1.62; P = .581). CONCLUSIONS: In a meta-analysis of randomized trials, we found that routine use of prophylactic clipping does not reduce risk of postpolypectomy bleeding overall. However, clipping appeared to reduce bleeding after removal of large (more than 20 mm) proximal lesions.

The Chloroplast of Chlamydomonas reinhardtii as a Testbed for Engineering Nitrogen Fixation into Plants.

Eukaryotic organisms such as plants are unable to utilise nitrogen gas (N2) directly as a source of this essential element and are dependent either on its biological conversion to ammonium by diazotrophic prokaryotes, or its supply as chemically synthesised nitrate fertiliser. The idea of genetically engineering crops with the capacity to fix N2 by introduction of the bacterial nitrogenase enzyme has long been discussed. However, the expression of an active nitrogenase must overcome several major challenges: the coordinated expression of multiple genes to assemble an enzyme complex containing several different metal cluster co-factors; the supply of sufficient ATP and reductant to the enzyme; the enzyme's sensitivity to oxygen; and the intracellular accumulation of ammonium. The chloroplast of plant cells represents an attractive location for nitrogenase expression, but engineering the organelle's genome is not yet feasible in most crop species. However, the unicellular green alga Chlamydomonas reinhardtii represents a simple model for photosynthetic eukaryotes with a genetically tractable chloroplast. In this review, we discuss the main advantages, and limitations, of this microalga as a testbed for producing such a complex multi-subunit enzyme. Furthermore, we suggest that a minimal set of six transgenes are necessary for chloroplast-localised synthesis of an 'Fe-only' nitrogenase, and from this set we demonstrate the stable expression and accumulation of the homocitrate synthase, NifV, under aerobic conditions. Arguably, further studies in C. reinhardtii aimed at testing expression and function of the full gene set would provide the groundwork for a concerted future effort to create nitrogen-fixing crops.

Clip Closure After Resection of Large Colorectal Lesions With Substantial Risk of Bleeding.

BACKGROUND & AIMS: It is not clear whether closure of mucosal defects with clips after colonic endoscopic mucosal resection (EMR) prevents delayed bleeding, although it seems to have no protective effects when risk is low. We performed a randomized trial to evaluate the efficacy of complete clip closure of large (≥2 cm) nonpedunculated colorectal lesions after EMR in patients with an estimated average or high risk of delayed bleeding. METHODS: We performed a single-blind trial at 11 hospitals in Spain from May 2016 through June 2018, including 235 consecutive patients who underwent EMR for large nonpedunculated colorectal lesions with an average or high risk of delayed bleeding (based on Spanish Endoscopy Society Endoscopic Resection Group score). Participants were randomly assigned to groups that received closure of the scar with 11-mm through-the-scope clips (treated, n = 119) or no clip (control, n = 116). The primary outcome was proportion of patients in each group with delayed bleeding, defined as evident hematochezia that required medical intervention within 15 days after colonoscopy. RESULTS: In the clip group, complete closure was achieved in 68 (57%) cases, with partial closure in 33 (28%) cases and failure to close in 18 (15%) cases. Delayed bleeding occurred in 14 (12.1%) patients in the control group and in 6 (5%) patients in the clip group (absolute risk difference, reduction of 7% in the clip group; 95% confidence interval, -14.7% to 0.3%). After completion of the clip closure, there was only 1 (1.5%) case of delayed bleeding (absolute risk difference, reduction of 10.6%; 95% confidence interval, -4.3% to 17.9%). CONCLUSIONS: In a randomized trial of patients with large nonpedunculated colorectal lesions undergoing EMR, we found that clip closure of mucosal defects in patients with a risk of bleeding can be a challenge, but also reduces delayed bleeding. Prevention of delayed bleeding required complete clip closure. ClinicalTrials.gov ID: NCT02765022.

Multigenic engineering of the chloroplast genome in the green alga Chlamydomonas reinhardtii.

The chloroplast of microalgae such as Chlamydomonas reinhardtii represents an attractive chassis for light-driven production of novel recombinant proteins and metabolites. Methods for the introduction and expression of transgenes in the chloroplast genome (=plastome) of C. reinhardtii are well-established and over 100 different proteins have been successfully produced. However, in almost all reported cases the complexity of the genetic engineering is low, and typically involves introduction into the plastome of just a single transgene together with a selectable marker. In order to exploit fully the potential of the algal chassis it is necessary to establish methods for multigenic engineering in which many transgenes can be stably incorporated into the plastome. This would allow the synthesis of multi-subunit proteins and the introduction into the chloroplast of whole new metabolic pathways. In this short communication we report a proof-of-concept study involving both a combinatorial and serial approach, with the goal of synthesizing five different test proteins in the C. reinhardtii chloroplast. Analysis of the various transgenic lines confirmed the successful integration of the transgenes and accumulation of the gene products. However, the work also highlights an issue of genetic instability when using the same untranslated region for each of the transgenes. Our findings therefore help to define appropriate strategies for robust multigenic engineering of the algal chloroplast.

Clinical validation of risk scoring systems to predict risk of delayed bleeding after EMR of large colorectal lesions.

BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).

Lactobacillus fermentum Administration Modulates Cytokine Expression and Lymphocyte Subpopulation Levels in Broiler Chickens Challenged with Campylobacter coli.

This investigation was performed to assess the supplementation of probiotics on cytokine expression and lymphocyte subpopulation in Campylobacter coli challenged chickens. Thirty-six individuals were equally separated into four experimental treatments: C = untreated chickens, LB = probiotic control (Lactobacillus fermentum), Cc = Campylobacter-challenged control, LBCc = probiotic + Cc. All chicks were slaughtered and cecum samples were collected on day 4 postinfection. Gene expression analysis, using reverse transcription quantitative PCR (RT-qPCR), revealed significant differences in cytokine transcript expression between untreated and probiotic-treated chickens. In addition, flow cytometry was used to quantitate the levels of lymphocyte subpopulations. Principal component analysis showed that probiotic administration induced an overall downregulation of cytokine expression. C. coli exposure provoked a similar response to that of L. fermentum but to a lesser extent. Colonization of C. coli in the presence of the probiotic evoked a complex response with an upregulation of some type II cytokines, including interleukin IL-4 and IL-13, which could explain the increased presence of antibodies in both lamina propria and epithelium. Moreover, despite that the percentage of CD8 intraepithelial lymphocytes (IELs) was found to be higher, downregulation of proinflammatory cytokines IL-15, IL-16, and interferon γ was observed. This suggests that the detected CD8 are not effector cells but induced IELs, which release antimicrobial peptides, and are ready to be primed upon encountering antigen. These outcomes demonstrate that probiotic administration promotes a humoral response to a C. coli infection while dampening any potential inflammation mediated by effector T cells in 1-week-old chicks.

Cancer immunotherapy-associated hypophysitis.

The advances in cancer therapy have included the development of drugs that inhibit immune checkpoint ligands. Two types of immune checkpoint inhibitors, both antibodies that target CTLA-4 and PD-1, have been approved for its use in NSCLC and melanoma as first-line or second-line therapy. Sadly, not desirable consequences of immunotherapy are immune-related adverse events. immune-related hypophysitis is the most common endocrine adverse event after thyroid disfunction. The particularity of endocrine immune-related adverse events is their non-reversibility, with incidence and prevalence destined to increase in the coming years, particularly if this form of therapy is used in the future for earlier stages of cancer. Therefore, hypophysitis represents a challenge for the physician, sometimes occurring without specific symptomatology and which should be considered for clinical management. In this review, we describe the current data regarding the pathophysiology and management for immune-related hypophysitis.

Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD.

OBJECTIVE: Outside clinical trials, the effectiveness of chromoendoscopy (CE) for long-standing IBD surveillance is controversial. We aimed to assess the effectiveness of CE for neoplasia detection and characterisation, in real-life. DESIGN: From June 2012 to 2014, patients with IBD were prospectively included in a multicentre cohort study. Each colonic segment was evaluated with white light followed by 0.4% indigo carmine CE. Specific lesions' features were recorded. Optical diagnosis was assessed. Dysplasia detection rate between expert and non-expert endoscopists and learning curve were ascertained. RESULTS: Ninety-four (15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and 503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female; mean disease duration: 17 years). Colonoscopies were performed with standard definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield for dysplasia was comparable between standard definition and high definition (51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and 94%, respectively. Endoscopic characteristics predictive of dysplasia were: proximal location, loss of innominate lines, polypoid morphology and Kudo pit pattern III-V. CONCLUSIONS: CE presents a high diagnostic yield for neoplasia detection, irrespectively of the technology and experience available in any centre. In vivo, CE optical diagnosis is highly accurate for ruling out dysplasia, especially in expert hands. Lesion characteristics can aid the endoscopist for in situ therapeutic decisions. TRIAL REGISTRATION NUMBER: NCT02543762.

Roadmaps and Detours: Active Chlorophyll- a Assessments of Primary Productivity Across Marine and Freshwater Systems.

Assessing phytoplankton productivity over space and time remains a core goal for oceanographers and limnologists. Fast Repetition Rate fluorometry (FRRf) provides a potential means to realize this goal with unprecedented resolution and scale yet has not become the "go-to" method despite high expectations. A major obstacle is difficulty converting electron transfer rates to equivalent rates of C-fixation most relevant for studies of biogeochemical C-fluxes. Such difficulty stems from methodological inconsistencies and our limited understanding of how the electron requirement for C-fixation (Φe,C) is influenced by the environment and by differences in the composition and physiology of phytoplankton assemblages. We outline a "roadmap" for limiting methodological bias and to develop a more mechanistic understanding of the ecophysiology underlying Φe,C. We 1) re-evaluate core physiological processes governing how microalgae invest photosynthetic electron transport-derived energy and reductant into stored carbon versus alternative sinks. Then, we 2) outline steps to facilitate broader uptake and exploitation of FRRf, which could transform our knowledge of aquatic primary productivity. We argue it is time to 3) revise our historic methodological focus on carbon as the currency of choice, to 4) better appreciate that electron transport fundamentally drives ecosystem biogeochemistry, modulates cell-to-cell interactions, and ultimately modifies community biomass and structure.

Distributed Fast Self-Organized Maps for Massive Spectrophotometric Data Analysis †.

Analyzing huge amounts of data becomes essential in the era of Big Data, where databases are populated with hundreds of Gigabytes that must be processed to extract knowledge. Hence, classical algorithms must be adapted towards distributed computing methodologies that leverage the underlying computational power of these platforms. Here, a parallel, scalable, and optimized design for self-organized maps (SOM) is proposed in order to analyze massive data gathered by the spectrophotometric sensor of the European Space Agency (ESA) Gaia spacecraft, although it could be extrapolated to other domains. The performance comparison between the sequential implementation and the distributed ones based on Apache Hadoop and Apache Spark is an important part of the work, as well as the detailed analysis of the proposed optimizations. Finally, a domain-specific visualization tool to explore astronomical SOMs is presented.

Endoscopic tattooing of colorectal neoplasms removed by laparoscopy: a proposal for selective marking.

BACKGROUND AND AIM: Preoperative endoscopic tattooing is an effective procedure to identify small intraoperative neoplasms. However, there are no defined criteria with regard to the indications for endoscopic tattooing of these lesions at the time of diagnosis. The aim of this study was to establish endoscopic criteria that allow the selection of patients who will need a tattoo during the diagnostic colonoscopy. METHODS: An ambispective study of patients undergoing laparoscopy due to a colorectal neoplasia who underwent endoscopic tattooing during the period from 2007-2013 and 2016-2017. According to the endoscopic description of the neoplasms, the classification was polypoid lesions, neoplasms occupying < 50% or ≥ 50% of the intestinal lumen and stenosing neoplasias. RESULTS: Tattooing of the lesion was performed in 120 patients and the same lesions were identified during surgery in 114 (95%) cases. Most of the neoplasias described as polypoids and neoplasias that occupied < 50% of the intestinal lumen were not visualized during surgery and therefore required a tattoo (33 of 42 and 18 of 26 respectively, p = 0.0001, X2). On the other hand, stenosing lesions or neoplasias occupying ≥ 50% of the intestinal lumen were mostly identified during surgery (15 of 15 and 36 of 37 respectively, p = 0.0001, X2) without the need for a tattoo. Overall, the identification of neoplasms according to established criteria was 98%. CONCLUSION: These results suggest that it is possible to establish endoscopic criteria that allow a successful selective tattooing during diagnostic endoscopy.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Clinical guidelines for endoscopic mucosal resection of non-pedunculated colorectal lesions. / Guía clínica para la resección mucosa endoscópica de lesiones colorrectales no pediculadas.

This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.

Physiopathology and genetics in aspirin-exacerbated respiratory disease.

INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) is a clinical entity characterized by hypersensitivity to aspirin leading to asthma and chronic rhinosinusitis with nasosinusal polyposis. The pathophysiology of the disease involves disruption at the level of arachidonic acid metabolism. Therefore, genetic association studies have been focused on the genes coding this pathway. As other mechanisms involved in the genesis of the disease were elucidated, the corresponding genes were also explored. AIM: To describe the association reported in the literature between gene polymorphisms involved in the pathophysiology or therapeutic processes of AERD. RESULTS: There is a genetic association between polymorphisms of genes involved in the synthesis of proteins related to arachidonic acid metabolism (LTC4S, ALOX5), antigen presentation (HLA), inflammation (IL5, IL17), and aspirin metabolism (CYP2C19). CONCLUSIONS: Genetic association research in AERD has evaluated studies of SNPs in metabolic pathways related to arachidonic acid. Recently, whole genome analysis strategies have allowed the detection of new genetic variants that were previously not considered. Furthermore, these studies have identified SNPs that are associated with inflammatory processes, which could serve as diagnostic markers or predictors of the therapeutic response.