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To determine whether there are differences in care experience of adolescent cancer patients and their main caregiver, treated in Adolescent Cancer Units (ACUs), compared to those treated in Non-Adolescent Cancer Units (NACUs), including the COVID-19 pandemic period.

•NGS-based stratification refines risk classification in T-ALL.•NGS classifier combined with MRD and WBC identifies a group of patients with a very high risk of relapse.

Since the introduction of post-transplantation cyclophosphamide (PTCy), haploidentical hematopoietic stem cell transplantation (haploSCT) has become a real alternative for patients who lack other eligible donors. The standard graft-versus-host disease (GVHD) prophylaxis after PTCy has been a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) (up to day +35), but promising results with sirolimus (with or without MMF) and single-agent tacrolimus have been published recently. This multicenter retrospective study compared the outcomes of 372 adult haploSCT recipients who received conditioning with thiotepa, busulfan, and fludarabine (TBF), PTCy, and additional GVHD prophylaxis with 1 of 3 strategies: cohort A, single-agent tacrolimus (n = 222); cohort B, CNI + MMF (n = 49); or cohort C, sirolimus + MMF (n = 101). No differences among the 3 cohorts were found in terms of grade II-IV acute GVHD (20% in cohort A, 25% in cohort B, and 30% in cohort C) or grade III-IV acute GVHD (9%, 6%, and 15%, respectively) at 100 days; however, cohort A had the lowest incidence of overall chronic GVHD (24%, 47%, and 52%, respectively; P= .001) and moderate-severe chronic GVHD (13%, 35%, and 33%, respectively; P= .001). There were no differences in 3-year overall survival, progression-free survival, nonrelapse mortality, or relapse among the 3 cohorts. Overall, our study suggests that single-agent tacrolimus, CNI + MMF, and sirolimus + MMF GVHD prophylaxis lead to similar outcomes following haploSCT with TBF and PTCy, with a low incidence of grade III-IV acute GVHD, although possible differences in chronic GVHD require further investigation.

Catalytic additives able to accelerate the lithium–sulfur redox reaction are a key component of sulfur cathodes in lithium–sulfur batteries (LSBs). Their design focuses on optimizing the charge distribution within the energy spectra, which involves refinement of the distribution and occupancy of the electronic density of states. Herein, beyond charge distribution, we explore the role of the electronic spin configuration on the polysulfide adsorption properties and catalytic activity of the additive. We showcase the importance of this electronic parameter by generating spin polarization through a defect engineering approach based on the introduction of Co vacancies on the surface of CoSe nanosheets. We show vacancies change the electron spin state distribution, increasing the number of unpaired electrons with aligned spins. This local electronic rearrangement enhances the polysulfide adsorption, reducing the activation energy of the Li–S redox reactions. As a result, more uniform nucleation and growth of Li2S and an accelerated liquid–solid conversion in LSB cathodes are obtained. These translate into LSB cathodes exhibiting capacities up to 1089 mA h g–1at 1 C with 0.017% average capacity loss after 1500 cycles, and up to 5.2 mA h cm–2, with 0.16% decay per cycle after 200 cycles in high sulfur loading cells.

Adherence to Helicobacter pylori (H. pylori)eradication treatment is a cornerstone for achieving adequate treatment efficacy. To determine which factors influence compliance with treatment. A systematic prospective non‐interventional registry (Hp‐EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG‐REDCap e‐CRF and were subjected to quality control. Modified intention‐to‐treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non‐compliance rate was higher in patients prescribed longer regimens (10‐, 14‐days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non‐adherence was lower for first‐line treatment than for rescue treatment (1.5% vs. 2.2%; p< 0.001). Differences in non‐adherence in the three most frequent first‐line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non‐compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p< 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2–7.7]; p< 0.001). Compliance with Helicobacter pylorieradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue‐treatment, prolonged treatment regimens, the presence of adverse events, and the use of non‐bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1)gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Le Collège national des enseignants de cancérologie (CNEC) a été créé en septembre 1986. Il a pour missions de développer l’enseignement de la cancérologie, de promouvoir les actions pédagogiques de la discipline, de participer à l’élaboration du contenu des enseignements et de la définition des cursus et du contrôle des connaissances pour la formation des étudiants en médecine et des spécialistes, d’élaborer et valider des documents pédagogiques relatifs aux enseignements ci-dessus, d’assurer la représentation de l’enseignement de l’oncologie auprès du Conseil National Universitaire (CNU) et des autorités administratives, d’assurer et coordonner les relations avec les autres disciplines universitaires, les sociétés savantes, les groupes professionnels nationaux, européens et internationaux, et de contribuer au développement de la recherche dans la discipline. Le bureau actuel a été élu en septembre 2022 pour trois ans.

Management of Helicobacter pylori(H. pylori) infection requires co‐treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylorieradication treatments based on the ‘European Registry on Helicobacter pylorimanagement’ (Hp‐EuReg). Hp‐EuReg is a multicentre, prospective, non‐interventionist, international registry on the routine clinical practice of H. pylorimanagement by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first‐line‐modified intention‐to‐treat effectiveness was achieved with the following treatments: (1) 14‐day therapies with clarithromycin‐amoxicillin‐bismuth and metronidazole‐tetracycline‐bismuth, both independently of the PPI dose prescribed; (2) All 10‐day (except 10‐day standard triple therapy) and 14‐day therapies with high‐dose PPIs; and (3) 10‐day quadruple therapies with clarithromycin‐amoxicillin‐bismuth, metronidazole‐tetracycline‐bismuth, and clarithromycin‐amoxicillin‐metronidazole (sequential), all with standard‐dose PPIs. In first‐line treatment, optimal effectiveness was obtained with high‐dose PPIs in all 14‐day treatments, in 10‐ and 14‐day bismuth quadruple therapies and in 10‐day sequential with standard‐dose PPIs. Optimal second‐line effectiveness was achieved with (1) metronidazole‐tetracycline‐bismuth quadruple therapy for 14‐ and 10 days with standard and high‐dose PPIs, respectively; and (2) levofloxacin‐amoxicillin triple therapy for 14 days with high‐dose PPIs. None of the 7‐day therapies in both treatment lines achieved optimal effectiveness. We recommend, in first‐line treatment, the use of high‐dose PPIs in 14‐day triple therapy and in 10‐or 14‐day quadruple concomitant therapy in first‐line treatment, while standard‐dose PPIs would be sufficient in 10‐day bismuth quadruple therapies. On the other hand, in second‐line treatment, high‐dose PPIs would be more beneficial in 14‐day triple therapy with levofloxacin and amoxicillin or in 10‐day bismuth quadruple therapy either as a three‐in‐one single capsule or in the traditional scheme.

An approach to economic dynamics in 5th-Century internal Africa: the contribution of the study of fine ceramic ware from the city of Ammaedara (Haïdra, Tunisia) Over the last few decades, advances in studies of the African economy have made it possible to qualify models that had long been accepted. Until recently, most of our knowledge came from the products of the great Mediterranean trade, amphora and African Red Slip wares, but work carried out in the inner regions of Africa has demonstrated the existence of an intraprovincial trade fuelled by continental ceramic productions, from the second half of the 2nd century to at least the Vandal period. This economic pattern, which has been highlighted by surveys and rare excavations, still raises many questions about the trade routes to and within these regions. The study of fine wares from the ancient city of Ammaedara/Haïdra (Tunisian High Steppes) provides new data on economy and patterns of consumption Inland regions of Roman Africa.

The Matterhorn, a famous mountain in the Swiss Alps is a well characterized geomorphosite, presenting both an important scientific interest and aesthetic, cultural and economic values in Switzerland. The main scientific issues concerning the Matterhorn are its place in the tectonic history of the Alps, the carving of a residual pyramid by glacial erosion and the effects of melting of high mountain permafrost on mountaineering. To answer those questions, two “tools” were used, the field work and the bibliographic investigations. The Matterhorn played, from its first ascent in 1865 until today, a very special role in the history of mountaineering, and its remarkable shape has become iconic in Switzerland. As a consequence, the Matterhorn can be analyzed through four time scales:(1) the deep time of tectonics during the Cenozoic era, which saw the thrusting and piling up of the “Pennine nappes,” due to the collision between African and European plates; (2) the Quaternary period of glacial erosion, which carved the Matterhorn into its distinctive pyramidal peak shape;(3) the Anthropocene time of the thawing of high mountain permafrost; and (4) the era of humans or mountaineering, which spans over than 150 years, from the first ascent in 1865 to the recent achievements of modern mountaineering.

•In adult KMT2A-r BCP-ALL, TP53and IKZF1alterations are associated with very poor outcome.•KMT2Agenomic fusion should be the preferred MRD marker over IG/TRto assess early treatment response and predict long-term outcome.

In France, the prevalence of hypertension is higher than 30%. Although treatment guidelines have been well established over the last twenty years, the national blood pressure control rate is below the average of high-income countries. This observational study aimed to describe the antihypertensive prescription behaviours of primary care physicians (PCPs) in France and to assess their compliance with current French guidelines, focusing on three specific prescription issues and their potential repercussions on blood pressure control: treatment initiation, treatment renewal or change and type of triple therapy. Prescription data were retrieved using the IQVIA longitudinal patient database (LPD), which delivers real-world data insights from French primary care electronic medical records (EMR). The average number of prescribed therapeutic agents was 1.9 per patient, with 39.3% monotherapy prescriptions. Treatment initiation represented 7.2% of all antihypertensive prescriptions. At treatment initiation, 22.5% of patients were prescribed dual therapy. The proportion of treatment renewal in the same therapeutic class was 74.3% while the proportion of treatment change was 18.5%. Of these, only 6.3% of patients received an additional therapy. Lastly, 35.7% of triple therapies were consistent with the recommended combinations. In conclusion, this study provides evidence of therapeutic gaps in hypertension management in France. The low blood control rate may be attributed to PCPs’ therapeutic inertia and lack of knowledge of treatment guidelines. All stakeholders should commit to rapid corrective action in order to provide patients with the best care.

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Plants simultaneously interact with belowground symbionts such as arbuscular mycorrhizal (AM) fungi and aboveground antagonists such as aphids. Generally, plants gain access to valuable resources including nutrients and water through the AM symbiosis and are more resistant to pests. Nevertheless, aphids’ performance improves on mycorrhizal plants, and it remains unclear whether a more nutritious food source and/or attenuated defenses are the contributing factors. This study examined the shoot and root transcriptome of barrel medic (Medicago truncatulaGaertn.) plants highly colonized by the AM fungus Rhizophagus irregularis(Blaszk., Wubet, Renker, and Buscot) C. Walker and A. Schüßler (Glomerales: Glomeraceae) and exposed to 7 days of mixed age pea aphid (Acyrthosiphon pisum(Harris)) herbivory. The RNA-seq samples chosen for this study showed that aphids were heavier when fed mycorrhizal plants compared to nonmycorrhizal plants. We hypothesized that (i) insect-related plant defense pathways will be downregulated in shoots of mycorrhizal plants with aphids compared to nonmycorrhizal plants with aphids; (ii) pathways involved in nutrient acquisition, carbohydrate-related and amino acid transport will be upregulated in shoots of mycorrhizal plants with aphids compared to nonmycorrhizal plants with aphids; and (iii) roots of mycorrhizal plants with aphids will exhibit mycorrhiza-induced resistance. The transcriptome data revealed that the gene repertoire related to defenses, nutrient transport, and carbohydrates differs between nonmycorrhizal and mycorrhizal plants with aphids, which could explain the weight gain in aphids. We also identified novel candidate genes that are differentially expressed in nonmycorrhizal plants with aphids, thus setting the stage for future functional studies.

Structured Graphical Abstract

The presence of >94% classical monocytes (MO1, CD14++/CD16‐) in peripheral blood (PB) has an excellent performance for the diagnosis of chronic myelomonocytic leukemia (CMML). However, the monocyte gating strategy is not well defined. The objective of the study was to compare monocyte gating strategies and propose an optimal one. This is a prospective, single center study assessing monocyte subsets in PB. First, we compared monocyte subsets using 13 monocyte gating strategies in 10 samples. Then we developed our own 10 color tube and tested it on 124 patients (normal white blood cell counts, reactive monocytosis, CMML and a spectrum of other myeloid malignancies). Both conventional and computational (FlowSOM) analyses were used. Comparing different monocyte gating strategies, small but significant differences in %MO1 and percentually large differences in %MO3 (nonclassical monocytes) were found, suggesting that the monocyte gating strategy can impact monocyte subset quantification. Then, we designed a 10‐color tube for this purpose (CD45/CD33/CD14/CD16/CD64/CD86/CD300/CD2/CD66c/CD56) and applied it to 124 patients. This tube allowed proper monocyte gating even in highly abnormal PB. Computational analysis found a higher %MO1 and lower %MO3 compared to conventional analysis. However, differences between conventional and computational analysis in both MO1 and MO3 were globally consistent and only minimal differences were observed when comparing the ranking of patients according to %MO1 or %MO3 obtained with the conventional versus the computational approach. The choice of monocyte gating strategy appears relevant for the monocyte subset distribution test. Our 10‐color proposal allowed satisfactory monocyte gating even in highly abnormal PB. Computational analysis seems promising to increase reproducibility in monocyte subset quantification.

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants.

The high-throughput quantification of intact proteoforms using a label-free approach is typically performed on proteins in the 0–30 kDa mass range extracted from whole cell or tissue lysates. Unfortunately, even when high-resolution separation of proteoforms is achieved by either high-performance liquid chromatography or capillary electrophoresis, the number of proteoforms that can be identified and quantified is inevitably limited by the inherent sample complexity. Here, we benchmark label-free quantification of proteoforms of Escherichia coliby applying gas-phase fractionation (GPF) via field asymmetric ion mobility spectrometry (FAIMS). Recent advances in Orbitrap instrumentation have enabled the acquisition of high-quality intact and fragmentation mass spectra without the need for averaging time-domain transients prior to Fourier transform. The resulting speed improvements allowed for the application of multiple FAIMS compensation voltages in the same liquid chromatography–tandem mass spectrometry experiment without increasing the overall data acquisition cycle. As a result, the application of FAIMS to label-free quantification based on intact mass spectra substantially increases the number of both identified and quantified proteoforms without penalizing quantification accuracy in comparison to traditional label-free experiments that do not adopt GPF.

Le cancer gastrique est le sixième cancer le plus fréquent dans le monde. Les adénocarcinomes gastriques peuvent être divisés en deux groupes : les adénocarcinomes de la jonction œsogastrique et les adénocarcinomes gastriques distaux, dont les facteurs de risque sont différents et pour lesquels la prise en charge thérapeutique peut varier. La stratégie de prise en charge des adénocarcinomes œsogastriques associe plusieurs modalités thérapeutiques. Celle des adénocarcinomes gastriques repose sur une chirurgie avec une chimiothérapie péri-opératoire. Les adénocarcinomes de la jonction œsogastrique peuvent être soit pris en charge chirurgicalement après une chimioradiothérapie néoadjuvante, soit être pris en charge de la même façon que les adénocarcinomes gastriques avec une chimiothérapie péri-opératoire. Il n’existe actuellement pas de preuve de la supériorité de l’une ou l’autre stratégie. Récemment, le nivolumab a été validé en adjuvant pour les patients ayant un cancer de l’œsophage, ayant eu une chimioradiothérapie préopératoire et présentant un résidu tumoral sur la pièce opératoire. En cas d’absence de traitement préopératoire, une chimioradiothérapie ou une chimiothérapie adjuvante pourront être discutées au cas par cas. Il n’existe pour l’instant pas de place pour les thérapies ciblées, ni pour l’adaptation du traitement postopératoire en fonction de la réponse au traitement préopératoire. La seule place validée de l’immunothérapie est en traitement adjuvant des cancers de l’œsophage même si de nombreuses études sont en cours et risquent de faire changer les pratiques prochainement. Le but de cette revue est de faire une synthèse de la littérature concernant la prise en charge des adénocarcinomes œsogastriques localisés.

abstract:Most contemporary decentralization has occurred at the local (district) rather than the regional (provincial) level. Why? The authors advance a theory highlighting the political incentives of central authorities to bypass the regional tier of government in favor of decentralizing to smaller, more fragmented units. Regional decentralization can capitalize on economies of scale and scope in public service provision, but it also enables political opposition to scale more effectively. Local decentralization provides some of the benefits of regional decentralization at less political risk, making it an imperfect but attractive substitute for central authorities. Drawing on cases from Africa and Latin America, this article discusses when and how strategic local decentralization can be an effective strategy to maintain political control in divided societies, why sometimes governments may instead opt for regional decentralization or (re)centralization, and how the choice of decentralization level depends on political geography and history as well as economic factors.

Graphical Abstract

Background: The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle. Results: Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested. Conclusions: We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.

Previous literature has analyzed the effect of internet disclosure on NPO donations, specifically, through website disclosure, showing a positive relation between internet disclosure and NPO income. Nonetheless, there is a lack of studies examining the association between sentiment on social media and NPO donations. Therefore, the aim of this study is to examine the effect that sentiment in Twitter messages has on the donations received by NPOs. Using a sample of NPOs listed on the Non-Profit Times 100, we examine whether the sentiment transmitted by the NPOs through Twitter affects their donations. The results show that the sentiment associated with certain specific categories of messages (community messages and information messages about matters not directly related to the NPO) has a significant effect on the amount of donations received.

This study aims to know how fluid intelligence and linguistic attitude participate in the language learning of young people who are in a linguistic immersion situation in Catalonia. Considering the linguistic particularities of the Catalan territory, a path model has been designed in which the effect of the fluid intelligence and linguistic attitude on the acquisition of the two official languages of the territory (Spanish and Catalan) in young immigrants of Romanian origin is studied. The results show how fluid intelligence exerted a significant facilitating effect of medium-low magnitude on learning of similar intensity for both languages. However, the attitude shows to exert a significant facilitating effect of low magnitude for the acquisition of the vehicular language (Catalan), but not significant for the language of non-academic use (Spanish). These results suggest that fluid intelligence and linguistic attitude are facilitating agents of language acquisition in situations of linguistic immersion, although in the case of attitude, the intensity of this effect may depend on the way in which learners are in contact with the language.

Background: Hip fractures in amputees pose a significant challenge for the orthopedic surgeon due to technical difficulties and there is no standardisation in their management. Their treatment is consequently left to the surgeon’s ingenuity. The aim of this study is to describe the clinical characteristics and outcome of a series of hip fractures in lower limb amputees. Methods: A total of 12 patients and 15 hip fractures in lower limb amputees were included. Amputations below the malleoli and prosthetic surgery due to osteoarthritis constitute the exclusion criteria. Demographic, amputation-related and fracture data as well as radiological, functional, and clinical outcomes were collected through the patients' medical records. Results: Age at fracture and at amputation were different depending on the cause of amputation. Most patients (10/12) were male. Seven patients had an infracondylar amputation and five patients had a supracondylar amputation. Ten hip fractures were on the same side of the amputation, three were contralateral and one was bilateral. Pertrochanteric (6/15) and subcapital (5/15) were the main types observed. Different traction methods and surgical procedures were used. We observed no significant differences in terms of outcome regardless of the fracture, traction method, and surgical management. No complications related to surgery or during follow-up were found. Mortality at one year postoperatively was absent. Conclusion: Provided an experienced orthopaedic surgeon, a pre-operative assessment, a comprehensive surgical planning, and a multidisciplinary rehabilitation strategy are present; a satisfactory outcome is to be expected.

ObjectivesTo evaluate, with a cardiopulmonary exercise test (CPET), the cardiopulmonary fitness of children with asthma, in comparison to healthy controls, and to identify the clinical and CPET parameters associated with the maximum oxygen uptake (VO2max) in childhood asthma.DesignThis cross-sectional controlled study was carried out in CPET laboratories from two tertiary care paediatric centres. The predictors of VO2maxwere determined using a multivariable analysis.ResultsA total of 446 children (144 in the asthma group and 302 healthy subjects) underwent a complete CPET. Mean VO2maxwas significantly lower in children with asthma than in controls (38.6±8.6 vs 43.5±7.5 mL/kg/min; absolute difference (abs. diff.) of −4.9 mL/kg/min; 95% CI of (−6.5 to −3.3) mL/kg/min; p<0.01) and represented 94%±9% and 107%±17% of predicted values, respectively (abs. diff. −13%; 95% CI (−17 to −9)%; p<0.01). The proportion of children with an impaired VO2maxwas four times higher in the asthma group (24% vs 6%, p<0.01). Impaired ventilatory efficiency with increased VE/VCO2slope and low breathing reserve (BR) were more marked in the asthma group. The proportion of children with a decreased ventilatory anaerobic threshold (VAT), indicative of physical deconditioning, was three times higher in the asthma group (31% vs 11%, p<0.01). Impaired VO2maxwas associated with female gender, high body mass index (BMI), FEV1, low VAT and high BR.ConclusionCardiopulmonary fitness in children with asthma was moderately but significantly altered compared with healthy children. A decreased VO2maxwas associated with female gender, high BMI and the pulmonary function.Trial registration numberNCT04650464.

Unstable cavities are defined as cavities with cerumen accumulation that need frequent cavity cleaning in the out-patient clinic, cavities that are intolerant to water due to risk of infection or that are subject to frequent infection and otorrhoea. The objective of this study is to address the problem of troublesome mastoid cavities, with the performance of secondary mastoid obliteration and canal wall reconstruction, using a novel posterior auricular artery (PAA) fascia-periosteum flap.

Evaluar los resultados oncológicos y el perfil de seguridad de un régimen de Bacilo Calmette-Guérin (BCG) de dosis reducida frente a uno de dosis completa en pacientes con cáncer de vejiga no músculo infiltrante (CVNMI).

ObjectiveTo evaluate the use, effectiveness and safety of Helicobacter pyloriempirical rescue therapy in third and subsequent treatment lines in Europe.DesignInternational, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis.ResultsOverall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%.ConclusionEmpirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update.Trial registration numberNCT02328131.

Este estudio pretende conocer el modo en que la inteligencia fluida y la actitud lingüística participan en el aprendizaje lingüístico de los jóvenes que se encuentran en situación de inmersión lingüística en Cataluña. Considerando las particularidades lingüísticas del territorio catalán, se ha diseñado un modelo path en el que se estudia el efecto de la inteligencia fluida y actitud lingüística sobre la adquisición de las dos lenguas oficiales del territorio (castellano y catalán) en jóvenes inmigrantes de origen rumano. Los resultados muestran que la inteligencia fluida ejerce un efecto facilitador significativo de magnitud media-baja sobre el aprendizaje de intensidad similar para ambas lenguas. Sin embargo, la actitud muestra ejercer un efecto facilitador significativo de baja magnitud para la adquisición de la lengua vehicular (catalán), pero no significativo para la lengua de uso no académico (castellano). Estos resultados sugieren que la inteligencia fluida y la actitud lingüística resultan agentes facilitadores de la adquisición del lenguaje en situación de inmersión lingüística, aunque en el caso de la actitud la intensidad de este efecto puede depender del modo en que los aprendices están en contacto con la lengua.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes.

Le leucemie mieloidi acute (LMA) negli adulti rappresentano un gruppo di emopatie risultanti dalla trasformazione oncogenica dei progenitori ematopoietici. Anche se la loro modalità di rivelazione è relativamente stereotipata, contrassegnata in primo piano da un’insufficienza midollare, più raramente da una sindrome tumorale, si tratta di un insieme di entità molto eterogenee. La diagnosi richiede una valutazione sofisticata che combina studi citogenetici, immunofenotipici e molecolari alla base della nuova classificazione dell’Organizzazione Mondiale della Sanità (OMS). La citogenetica e la tipizzazione molecolare sono particolarmente importanti per la prognosi delle LMA, aiutando a guidare i trattamenti, comprese le terapie mirate e le indicazioni per il trapianto di cellule staminali ematopoietiche. Il livello di risposta alla chemioterapia è anche apprezzato meglio con la biologia molecolare e la citometria a flusso che permette di quantificare la malattia residua minima il cui impatto prognostico è significativo. Le strategie terapeutiche utilizzate nei soggetti giovani o in grado di ricevere trattamenti intensivi sono adattate al rischio di ricaduta e si basano su una chemioterapia intensiva e su un trapianto di cellule staminali ematopoietiche. Nei soggetti più anziani o non eleggibili a un trattamento intensivo, la prognosi rimane molto sfavorevole, anche se sono stati osservati progressi recenti in seguito all’arrivo di un inibitore di BCL2 in combinazione con trattamenti a bassa intensità. I punteggi di comorbilità oncogeriatrica possono aiutare nella decisione terapeutica. Infine, la decifrazione molecolare delle LMA ha rivelato anomalie oncogeniche ricorrenti accessibili a terapie mirate come gli inibitori della tirosin-chinasi FLT3, l’isocitrato deidrogenasi (IDH1/2) o la proteina antiapoptotica BCL2. Questo articolo, sintetizzando gli aspetti clinici di base, i nuovi fattori prognostici e i principi di gestione terapeutica, vuole aiutare gli studenti, i medici di medicina generale o gli specialisti non ematologi ad avere una visione d’insieme dell’argomento e consentirà loro di acquisire nozioni di base per la diagnosi, per la gestione terapeutica talora urgente e per una migliore informazione dei pazienti e dei loro familiari.

Posttraumatic stress disorder (PTSD) is a heritable (h2= 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P= 6.3 × 10−8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P= 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q< 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Les interactions médicamenteuses (IM) sont un problème prépondérant dans les prescriptions. Dix à 30 % des IM entraînent un événement indésirable notamment par diminution de l’absorption des médicaments. Les conséquences cliniques sont importantes lorsqu’il s’agit d’anticancéreux, d’antibiotiques ou d’antirétroviraux. En regard de la fréquence des IM, les interventions pharmaceutiques (IP) qui leur sont dédiées sont moins fréquentes que les autres types d’IP. Les systèmes d’aide à la décision pharmaceutique (SADP) se développent pour améliorer la détection et la résolution des problèmes liés à la pharmacothérapie (PLP).

Immune monitoring in cancer immunotherapy involves screening CD8+ T-cell responses against neoantigens, the tumor-specific peptides presented by Major histocompatibility complex Class I (MHCI) on the cell surface. High-throughput immune monitoring requires methods to produce and characterize small quantities of thousands of MHCI–peptide complexes that may be tested for a patient’s T-cell response. MHCI synthesis has been achieved using a photocleavable peptide that is exchanged by the neoantigen; however, assays that measure peptide exchange currently disassemble the complex prior to analysis─precluding direct molecular characterization. Here, we use native mass spectrometry (MS) to profile intact recombinant MHCI complexes and directly measure peptide exchange. Coupled with size-exclusion chromatography or capillary-zone electrophoresis, the assay identified all tested human leukocyte antigen (HLA)/peptide combinations in the nanomole to picomole range with minimal run time, reconciling the synthetic and analytical requirements of MHCI–peptide screening with the downstream T-cell assays. We further show that the assay can be “multiplexed” by measuring exchange of multiple peptides simultaneously and also enables calculation of Vc50, a measure of gas-phase stability. Additionally, MHCI complexes were fragmented by top-down sequencing, demonstrating that the intact complex, peptide sequence, and their binding affinity can be determined in a single analysis. This screening tool for MHCI–neoantigen complexes represents a step toward the application of state-of-the-art MS technology in translational settings. Not only is this assay already informing on the viability of immunotherapy in practice, the platform also holds promise to inspire novel MS readouts for increasingly complex biomolecules used in the diagnosis and treatment of disease.

AbstractThis paper describes a set of theoretical and practical aspects related to the modelling of cracking in axially reinforced concrete members subjected to pure tension accounting for size effects. In particular, the paper describes a new methodology to achieve a probabilistic description of the crack’s spacing using a spatially correlated Weibull random field coupled to an energetic-statistical size effect law. Such aspects do not seem to be significantly covered in existing studies; although the mean and maximal crack spacing values are systematically of interest to control the cracking state in reinforced concrete structures. The proposed approach is validated based on a set of tests performed by Farra and Jacoud (1993). Finally, the stochastic model is used to define a meta-model of the mean and maximal crack spacing values. Such explicit formulations are intended for engineering applications and involve explicitly size effect parameters. In that sense, they are an evolution of the current regulatory formulae in the Eurocode or the Model Codes (where size effects are overlooked).

To provide practical recommendations for the management of mineral and bone metabolism alterations in pregnancy and lactation. Participants: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition.

This randomized controlled trial is the highest-evidence study to date on en bloc resection of bladder tumor (ERBT). ERBT was noninferior to the conventional transurethral resection technique in the staging of bladder cancer. The rate of T1 substaging feasibility was significantly higher in the ERBT group. Intraoperative and postoperative outcomes were comparable between the groups, and oncological outcomes were comparable at median follow-up of 15 mo.

Proporcionar unas recomendaciones prácticas para el manejo de las alteraciones del metabolismo mineral y óseo en la gestación y la lactancia. Participantes: Miembros del Grupo de Metabolismo Mineral de la Sociedad Española de Endocrinología y Nutrición.