Notes

Whole-blood metabolomics of dementia sufferers expose classes regarding disease-linked metabolites.
ing their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.Selenium (Se) is essential for selenoprotein synthesis, being thus important for immune and thyroid function, and for antioxidant defence. Some studies have shown that low levels of Se may associate with hypertensive disorders of pregnancy (HDP). Nevertheless, evidence supporting Se supplementation in pregnant or childbearing-age women is still lacking. In this context, this work aimed to systematically review the most recent scientific evidence to understand the relationship between Se levels and HDP. We performed a systematic review (protocol number CRD42022310424) with literature of the last decade. PubMed, Scopus, Web of Science, registers and grey literature were searched to identify studies reporting measurement of Se levels in normotensive and hypertensive pregnant women (supplemented or not with Se). Study quality was assessed using the National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Among the thirty included studies, a majority, 61 % (n 19) of the 'good' or 'fair' studies, reported a negative association between Se and HDP, and some studies, 39 % (n 11) of the 'good' or 'fair' studies, reported a lack of association. This review provides an important amount of quality evidence suggesting that low Se levels associate with the occurrence of HDP. Nevertheless, the gathered information is not enough to underlie a recommendation for Se supplementation in pregnancy to protect against HDP. Thus, this review emphasises the need for further well-designed randomised controlled trials that may provide blunt evidence regarding the benefits of Se supplementation during pregnancy.Antiviral treatments against hepatitis B virus (HBV) suppress viral replication but do not eradicate the virus, and need therefore to be taken lifelong to avoid relapse. Mathematical models can be useful to support the development of curative anti-HBV agents; however, they mostly focus on short-term HBV DNA data and neglect the complex host-pathogen interaction. This work aimed to characterize the effect of treatment with lamivudine and/or pegylated interferon (Peg-IFN) in 1,300 patients (hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative) treated for 1 year. A mathematical model was developed incorporating two populations of infected cells, namely I 1 , with a high transcriptional activity, that progressively evolve into I 2 , at a rate δ tr , representing cells with integrated HBV DNA that have a lower transcriptional activity. Parameters of the model were estimated in patients treated with lamivudine or Peg-IFN alone (N = 894), and the model was then validated in patients treated with lamivudine plus Peg-IFN (N = 436) to predict the virological response after a year of combination treatment. Lamivudine had a larger effect in blocking viral production than Peg-IFN (99.4-99.9% vs. 91.8-95.1%); however, Peg-IFN had a significant immunomodulatory effect, leading to an enhancement of the loss rates of I 1 (×1.7 in HBeAg-positive patients), I 2 (> ×7 irrespective of HBeAg status), and δ tr (×4.6 and ×2.0 in HBeAg-positive and HBeAg-negative patients, respectively). Using this model, we were able to describe the synergy of the different effects occurring during treatment with combination and predicted an effect of 99.99% on blocking viral production. This framework can therefore support the optimization of combination therapy with new anti-HBV agents.Freshwater ecosystems are among the most endangered ecosystem in the world. Understanding how human activities affect these ecosystems requires disentangling and quantifying the contribution of the factors driving community assembly. While it has been largely studied in temperate freshwaters, tropical ecosystems remain challenging to study due to the high species richness and the lack of knowledge on species distribution. Here, the use of eDNA-based fish inventories combined to a community-level modelling approach allowed depicting of assembly rules and quantifying the relative contribution of geographic, environmental and anthropic factors to fish assembly. We then used the model predictions to map spatial biodiversity and assess the representativity of sites surveyed in French Guiana within the EU Water Framework Directive (WFD) and highlighted areas that should host unique freshwater fish assemblages. We demonstrated a mismatch between the taxonomic and functional diversity. Taxonomic assemblages between but also within basins were mainly the results of dispersal limitation resulting from basin isolation and natural river barriers. Contrastingly, functional assemblages were ruled by environmental and anthropic factors. The regional mapping of fish diversity indicated that the sites surveyed within the EU WFD had a better representativity of the regional functional diversity than taxonomic diversity. Importantly, we also showed that the assemblages expected to be the most altered by anthropic factors were the most poorly represented in terms of functional diversity in the surveyed sites. The predictions of unique functional and taxonomic assemblages could, therefore, guide the establishment of new survey sites to increase fish diversity representativity and improve this monitoring program.
Empty pelvis syndrome (EPS) is a source of considerable morbidity following total pelvic exenteration. None of the available methods have been universally successful in mitigating this problem. The aim of this work was to evaluate the safety and efficacy of the obstetric Bakri balloon in preventing empty pelvis syndrome.

This study was a combined prospective and retrospective study of all total pelvic exenterations for rectal cancers from a single institution performed between October 2013 and May 2022. Since December 2019 the Bakri balloon was used in all patients who provided consent. EPS within 90 days was the primary end point, and included bowel obstruction, pelvic collection and entero-perineal fistula. Comparison with those patients who did not have a Bakri balloon was performed.

Seventy-five patients with a Bakri balloon were compared with 96 patients without a balloon placed after pelvic exenteration. No patient experienced an untoward complication from balloon deployment. The incidence of EPS was 13.3% and 22.9% in the Bakri and no Bakri cohorts, respectively (p= 0.110). Every component of EPS was proportionally lower, without statistical significance. Based on point estimates, the number needed to treat to prevent EPS using the Bakri balloon was 10.

Use of the Bakri balloon was safe without serious adverse events. The incidence of EPS after total pelvic exenteration was not statistically different with the use of the Bakri balloon despite a 9.6% reduction. A larger comparative study is needed to evaluate the efficacy of the balloon.
Use of the Bakri balloon was safe without serious adverse events. The incidence of EPS after total pelvic exenteration was not statistically different with the use of the Bakri balloon despite a 9.6% reduction. A larger comparative study is needed to evaluate the efficacy of the balloon.Legislative and technological advancements over the past decade have given rise to the proliferation of healthcare data generated from routine clinical practice, often referred to as real-world data (RWD). These data have piqued the interest of healthcare stakeholders due to their potential utility in generating evidence to support clinical and regulatory decision making. In the oncology setting, studies leveraging RWD offer distinct advantages that are complementary to randomized controlled trials (RCTs). They also permit the conduct of investigations that may not be possible through prospective designs due to ethics or feasibility. AnacardicAcid Despite its promise, the use of RWD for the generation of clinical evidence remains controversial due to concerns of unmeasured confounding and other sources of bias that must be carefully addressed in the study design and analysis. To facilitate a better understanding of when RWD can provide reliable conclusions on drug effectiveness, we seek to conduct 10 RWD-based studies that emulate RCTs in oncology using a systematic, protocol-driven approach described herein. Results of this investigation will help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology.Two major oceanographic changes have recently propagated through several trophic levels in coastal areas of Southeast Greenland (SEG). Firstly, the amount of drift-ice exported from the Fram Strait and transported with the East Greenland Current (EGC) has decreased significantly over the past two decades, and a main tipping element (summer sea ice) has virtually disappeared since 2003 leading to a regime shift in oceanographic and ecological conditions in the region. The following 20-year period with low or no coastal sea ice is unique in the 200-year history of ice observations in the region, and the regime shift is also obvious in the volume of ice export through the Fram Strait after 2013. In the same period, the temperature of the EGC south of 73.5 N has increased significantly (>2°C) since 1980. Secondly, the warm Irminger Current, which advects warm, saline Atlantic Water into the region, has become warmer since 1990. The lack of pack ice in summer together with a warming ocean generated cascading effects on the ecosystem in SEG that are manifested in a changed fish fauna with an influx of boreal species in the south and the subarctic capelin further north. At higher trophic levels there has been an increase in the abundance of several boreal cetaceans (humpback, fin, killer, and pilot whales and dolphins) that are either new to this area or occur in historically large numbers. It is estimated that the new cetacean species in SEG are responsible for an annual predation level of 700,000 tons of fish. In addition, predation on krill species is estimated at >1,500,000 tons mainly consumed by fin whales. Simultaneously, there has been a reduction in the abundance and catches of narwhals and walruses in SEG and it is suggested that these species have been impacted by the habitat changes.Bioaccumulation is one of the three criteria for the PBT assessment of chemicals, where P stands for persistence, B for bioaccumulation, and T for toxicity, which is a cornerstone for the "Registration, Evaluation, Authorization, and Restriction of Chemicals" (REACH) in the EU. Registrants are required by REACH to submit data on bioaccumulation if the chemical is manufactured in and/or imported to the European Economic Area at more than 100 t/year. Most of the experimental bioaccumulation studies submitted were on the bioconcentration factor (BCF) and were conducted prior to 2012, before the OECD Test Guideline 305 on Bioaccumulation in Fish was updated. An analysis of the submitted data revealed that many of the experimental data, but also the data from QSARs and other calculation methods, underestimate the actual bioaccumulation potential of hydrophobic substances considerably. One of the main reasons in the nonexperimental studies is that the BCF is related there to the total concentration of the chemical in water and not to the dissolved chemical concentration.
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