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A pesquisa tem como intuito principal examinar o processo de reestruturação urbana de Xangai, sitiada na República Popular da China, no período de 1990 a 2024; a partir de elementos que interagem com as inovações e que almejam a prosperidade comum e o futuro compartilhado. Para isso, o texto aborda de forma descritiva e exploratória a revisão da literatura sobre a China, com enfoque na cidade de Xangai. Ressalta-se como o planejamento urbano e as reformas econômicas remodelaram a paisagem urbana e a alçaram a um dos três mais importantes centros financeiros da Ásia; e, apresenta como principais efeitos: a descentralização, a expansão e a renovação de estruturas urbanas. Verifica-se um processo de substituição do uso do solo urbano, com a recuperação de estruturas existentes e a reorientação para circulação do capital.

Abstract Background The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder. Methods The association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries. Results Data were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts. Conclusions A large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk.

Abstract This study investigated the prevalence and severity of lower urinary tract symptoms (LUTS) in children with spastic cerebral palsy (SCP) and evaluated the effect of selective dorsal rhizotomy (SDR) in alleviating these symptoms. The study also explored the correlation between postoperative LUTS improvement and intraoperative electrophysiological findings. Prospective data were collected from a consecutive cohort of 247 children with SCP who underwent SDR and were retrospectively analyzed. Pre- and post-operative assessments included muscle tone, motor function, LUTS and intraoperative electrophysiology data were analyzed. Preoperatively, 94 patients (38.1%) had LUTS, and the severity of LUTS negatively correlated with motor function (R=-0.32, P 20µV. SDR effectively reduces spasticity, improves motor function, and alleviates LUTS in most children with SCP. Intraoperative neurophysiology may predict improvements, warranting further research.

Abstract The CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental disorder characterized by early-onset epilepsy, intellectual disability, motor and visual dysfunctions. The causative gene is CDKL5, which codes for a kinase required for brain development. There is no cure for CDD patients; treatments are symptomatic and focus mainly on seizure control. Several pathogenic variants are loss-of-function, but recent studies suggest that the CDD phenotype is sensitive to the CDKL5 gene dosage. Therefore, mRNA-targeted correction strategies that respect the physiological regulation of CDKL5 could be a valid alternative to augmentative gene therapy. Nonsense mutations cause ~ 11% of CDD cases, and these patients might benefit from readthrough therapies. We proved that drug-mediated readthrough efficiently suppresses premature CDKL5 nonsense codons, but the recoded kinase remained highly hypomorphic, curtailing the translational value of this pharmacological approach. In this study we explored if the recently developed Anticodon-edited tRNAs (ACE-tRNAs) offer an alternative readthrough strategy for CDD. Transfecting cells expressing different CDKL5 nonsense variants, we demonstrated that ACE-tRNAs efficiently restore full-length kinase synthesis. The recoded CDKL5 is correctly localized and catalytically active, thereby bringing tRNA-based therapy back into the spotlight for future investigations to assess the efficacy of this approach in correcting the pathological phenotype of CDD.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only. Concentrations of most POPs are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The exceptions are per- and polyfluoroalkyl substances, with concentrations of some long-chain PFAS such as perfluorononanoic acid increasing in populations in Nunavik, Greenland and Sweden. This paper provides a more extensive summary of levels of contaminants in adults, pregnant women, and children across the Arctic than previous AMAP human health assessments, particularly for levels of long-chain PFAS, which are currently under consideration for inclusion in the Stockholm Convention.

Abstract Background Concentrations of plasma per and poly-fluoroalkyl substances (PFAS) are elevated in the Inuit population of Nunavik and may be causing adverse health effects. Respiratory health outcomes have been associated with PFAS, but have not been explored in Inuit communities. The aim of the study was to examine the association between PFAS and respiratory health outcomes, and the moderating role of nutritional biomarkers. Methods We included up to 1298 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Generalized regression models were used to estimate the associations between six individual PFAS congeners and four self-reported symptoms, four spirometry measures, and physician-diagnosed asthma. Outcomes associated with PFAS from single chemical models were further explored using Bayesian Kernel Machine Regression (BKMR). The modifying effect of n-3 PUFA in red blood cell quartiles and vitamin D deficiency were examined on the associations between PFAS and respiratory outcomes. Results PFNA and PFOS were associated with asthma (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12, 2.32; OR 1.45 95% CI 1.04, 2.03). PFOA, PFNA, PFDA and PFHxS were associated with a decrease in the ratio between the forced expiratory volume in the first second and forced vital capacity (FEV1/FVC). No associations were observed with self-reported respiratory symptoms. No associations were observed between a PFAS mixture and asthma. Some associations were modified by nutritional factors, namely, stronger associations between PFOA and PFHxS and asthma with lower n-3 PUFA levels and stronger associations between PFDA, PFUnDA and PFOS and FEV1/FVC with vitamin D deficiency. Conclusion These findings add to the growing literature on the impacts of PFAS on respiratory health, and the importance of their global regulation. Associations were modified by nutritional factors pointing to the nutritional value of traditional Inuit foods.

Abstract Background Severe coronary artery disease (CAD) represents an advanced arterial narrowing, often associated with critical complications like myocardial infarction and angina. This study aimed to comprehensively investigate determinants of severe and multi-vessel CAD manifestations. Methods One thousand nine hundred patients with severe and multivessel CAD (stenosis > 70%) were recruited along with 1,056 controls without stenosis. Associations using a genotyping panel comprising 159 Single Nucleotide Polymorphisms (SNPs) previously implicated in CAD pathogenesis were examined and these associations were replicated using the UK Biobank cohort (N = 29,970). Results The investigation identified 14 genetic associations with severe CAD, of which 7 were also associated with multivessel disease. Notably, PHACTR1 SNP (rs9349379*G) showed a higher association with severe and multivessel CAD in individuals aged ≤ 65, indicating a higher risk of early disease onset. Conversely, the APOC1/APOE SNP (rs445925*T) is associated with reduced susceptibility to severe CAD and multivessel disease in individuals aged over 65, indicating a persistent negative association. Conclusions Following replication of the associations in the large UK Biobank dataset, it was found that patients carrying the rs9349379*G variant in the PHACTR1 gene are at risk of developing severe or multivessel disease. Conversely, the rs445925*T variant in APOC1/APOE is associated with reduced susceptibility to severe CAD and multivessel disease, highlighting the significance of this genetic variant in these specific CAD presentations. This study contributes to a better understanding of CAD heterogeneity, paving the way for tailored management strategies based on genetic profiles.

Abstract A seed recovered during archaeological excavations of a cave in the Judean desert was germinated, with radiocarbon analysis indicating an age of 993 CE– 1202 calCE. DNA sequencing and phylogenetic analysis identified the seedling as belonging to the angiosperm genus Commiphora Jacq., sister to three Southern African Commiphora species, but unique from all other species sampled to date. The germinated seedling was not closely related to Commiphora species commonly harvested for their fragrant oleoresins including Commiphora gileadensis (L.) C.Chr., candidate for the locally extinct “Judean Balsam” or “Balm of Gilead” of antiquity. GC-MS analysis revealed minimal fragrant compounds but abundance of those associated with multi-target bioactivity and a previously undescribed glycolipid compound series. Several hypotheses are offered to explain the origins, implications and ethnobotanical significance of this unknown Commiphora sp., to the best of our knowledge the first identified from an archaeological site in this region, including identification with a resin producing tree mentioned in Biblical sources and possible agricultural relationship with the historic Judean Balsam.

Abstract Moiré structures formed by twisting three layers of graphene with two independent twist angles present an ideal platform for studying correlated quantum phenomena, as an infinite set of angle pairs is predicted to exhibit flat bands. Moreover, the two mutually incommensurate moiré patterns among the twisted trilayer graphene (TTG) can form highly tunable moiré quasicrystals. This enables us to extend correlated physics in periodic moiré crystals to quasiperiodic systems. However, direct local characterization of the structure of the moiré quasicrystals and of the resulting flat bands are still lacking, which is crucial to fundamental understanding and control of the correlated moiré physics. Here, we demonstrate the existence of flat bands in a series of TTGs with various twist angle pairs and show that the TTGs with different magic angle pairs are strikingly dissimilar in their atomic and electronic structures. The lattice relaxation and the interference between moiré patterns are highly dependent on the twist angles. Our direct spatial mappings, supported by theoretical calculations, reveal that the localization of the flat bands exhibits distinct symmetries in different regions of the moiré quasicrystals.

Abstract Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater‐derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.

Abstract Four commercial glass compositions were investigated to understand their mechanisms of alteration in light of the current and future regulations on food contact materials. Lead crystal (fine glassware), soda-lime (food and cosmetic containers), borosilicate (cookware) and barium glass (tableware) powders and slabs were altered for 3 years, in acetic acid (4% vol) at pH = 2.4 and 70 °C. The leaching solution was analyzed by ICP-AES while glass slabs were investigated by ToF-SIMS and Spectroscopic Ellipsometry. As a result, in acidic medium, the polymerization of the silicate network as well as the glass composition impacted the alteration rates and depleted depths of alkalis and earth-alkalis elements. Yet the rate of hydrolysis measured from the release of Si, remained similar under identical alteration conditions, whatever the glass structure and composition. For lead crystal glass, repolymerization of the silicate network was observed in the course of alteration.

Humans are exposed to toxic methylmercury mainly by consuming marine fish, in particular top predator species like billfishes or tunas. In seafood risk assessments, mercury is assumed to be mostly present as organic methylmercury in predatory fishes; yet high percentages of inorganic mercury were recently reported in marlins, suggesting markedly different methylmercury metabolism across species. We quantified total mercury and methylmercury concentrations in muscle of four billfish species from the Indian and the Pacific oceans to address this knowledge gap. We found low percentages of methylmercury in blue and black marlins (15 ± 7 %) compared to swordfish and striped marlin (89 ± 13 %), with no significant differences among ocean regions. This illustrates that billfishes exhibit species-specific methylmercury bioaccumulation patterns, likely related to unique selenium-dependent in vivo methylmercury demethylation capacities in muscle. Blue and black marlins therefore appeared generally safer for human consumption than swordfish and striped marlin regarding MeHg toxicological effects. Yet, no matter the species, the frequency of recommended weekly billfish meals decreased with increasing fish size, given that mercury naturally accumulates over time. When assessing potential risks of billfish consumption, we therefore recommend measuring methylmercury, rather than total mercury, and relying on a large number of samples to cover a broad range of fish sizes. This study calls for additional characterization of mercury speciation and bioavailability in billfishes to better understand the mechanisms driving species-specific differences of methylmercury detoxification, and to refine dietary advices associated to marine top predators consumption.

In recent years, the limits of electromagnetic side-channel attacks have been significantly expanded. However, while there is a growing literature on increasing attack distance or performance, the discovery of new phenomenons about compromising electromagnetic emanations remains limited. In this work, we identify a novel form of modulation produced by unintentional electromagnetic emanations: phase-modulated emanations. This observation allows us to extract a side-channel leakage that can be exploited to reveal secret cryptographic material. We introduce a technique allowing us to exploit this side-channel in order to perform a full AES key recovery, using cheap and common hardware equipment like a software-defined radio (SDR). Moreover, we demonstrate that the exploitation of this new phase leakage can be combined with traditional amplitude leakage to significantly increase attack performance. While investigating the underlying phenomenon causing this unintentional modulation, we identified several prior works that have approached similar exploitation – without being aware of each other. Creating a bridge between older and recent work, we unveil the relationship between digital jitter and signal phase shift in the context of side-channel attacks and fill the gap between prior works from various research fields.

Vaccination has played a key role in reducing the health burden of COVID-19, however, concern has been raised worldwide regarding risk compensation, a process whereby feelings of security arising from being vaccinated may lead people to reduce their engagement in other protective behaviours.We investigated whether vaccination led to risk compensation and whether this changed over time by conducting a repeated cross-sectional study at seven intervals over the initial months (February to September 2021) of the vaccine rollout in France. Participants (N = 14,003) completed an online survey measuring vaccination status, vaccination intention and engagement in four preventive behaviours: mask wearing, avoidance of physical contact, hand hygiene, and avoiding social gatherings. Risk compensation was measured indirectly by comparing levels of engagement in protective behaviours according to vaccination status, with those unvaccinated but intending to vaccinate serving as a baseline.Risk compensation did not occur systematically and was mostly observed towards the end of the vaccine rollout for two of the four protective behaviours: avoiding social gatherings (in July and September for fully-vaccinated participants (Adjusted Odds Ratio (AOR) = .72, p = .045; AOR = .54, p = .022, respectively) and wearing a mask (those vaccinated with one dose, in September: AOR = .48, p = .029)). Our findings suggest that whilst unlikely to impede the overall effectiveness of public health campaigns, risk compensation nonetheless merits attention when designing informed, targeted public health messages and policy.

Many Indigenous cultures conceptualize health wholistically, whereby physical, mental, spiritual and relational dimensions of health are interconnected. Yet, quantitative approaches to studying Indigenous health remain anchored in western perspectives, that separate the dimensions of health. This paper aims to operationalize a wholistic indicator of health based on the IQI model of Inuit health. Variables from the 2017 Nunavik Health Survey (N = 1196) were selected based on their representativeness of IQI model. Exploratory Latent Class Analysis (LCA) was used to identify wholistic health profiles. Once participants assigned to their health profile, sociodemographic characteristics were compared across profiles, and multinomial regression models were used to examine the relationship between community-level social determinants of health and the profiles. The LCA revealed three health profiles, labelled as “excellent”, “good” and “fair” based on the distribution of answers to the indicators. Nunavimmiut in “excellent” and “good” health were more likely to: rate their health positively; be over 30 years old; be in a relationship; and have participated or volunteered in community events. Nunavimmiut in ”fair” health tended to report lower levels of community cohesion, family relationships, and emotional support. Intergrating culturally relevant models of health can support improved health status assessments and identify opportunities for health promotion.

The 2021 Arctic Monitoring Assessment Program (AMAP)’s Human Health Assessment report presents a summary of the presence of contaminants in human populations across the circumpolar Arctic and provides an update to the previous assessment released in 2015. The primary objective of this paper is to summarise some of these findings by describing the current levels of metals across the Arctic, including key regional and temporal trends based on available national data and literature, and highlight knowledge gaps. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of mercury (Hg) were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada). Still, concentrations of several metals are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The 2021 AMAP human health assessment report and this paper provide an extensive summary of levels of metals and trace elements in adults, pregnant women, and children across the Arctic.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0–24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

The global use of pesticides is increasing; however, few studies have examined the exposure of current-use pesticide exposure in Inuit populations. Some current use pesticides are also capable of long-range transport, potentially increasing exposures to northern populations. The study aim was to analyse pesticide (chlorophenoxy, organophosphates, and pyrethroid pesticide) biomarker levels in pooled samples from an Inuit population in Nunavik, Quebec. Thirty pooled samples from the Qanuilirpitaa? 2017 survey (Q2017) from individuals aged 16–80 years were included. Creatinine-adjusted arithmetic (AM) were compared by sex, age, and region sub-groups, and geometric mean concentrations (GM) were compared to those in the Canadian Health Measures Survey (CHMS). Most analysed pesticide biomarkers were detected, and PNP (a metabolite of methyl and ethyl parathion), trans-DCCA (a metabolite of pyrethroids), and 3,5,6-TCP (a metabolite of chlorpyrifos) had the highest concentrations. Concentrations in Q2017 were largely similar to or less than CHMS concentrations. Although not significant, there was a general increase in 2,4-D (a chlorophenoxy biomarker), 3,5,6-TCP, 3-PBA (a metabolite of pyrethroids), and trans-DCCA with increasing age. Concentrations were also somewhat higher in females versus males, but these were not significant. Environmental exposures to current use pesticides were detected in Nunavik and concentrations were similar to or less than those in the general Canadian population. Regular monitoring of current use pesticide exposures is recommended given the increasing global use of pesticides.

Background Assessing the risk of subsequent self-harm after hospitalisation for COVID-19 is critical for mental health care planning during and after the pandemic. Aims This study aims to compare the risk of admission to hospital for self-harm within 12 months following a COVID-19 hospitalisation during the first half of 2020, with the risk following hospitalisations for other reasons. Method Using the French administrative healthcare database, logistic regression models were employed to analyse data from patients admitted to hospitals in metropolitan France between January and June 2020. The analysis included adjustments for sociodemographic factors, psychiatric history and the level of care received during the initial hospital stay. Results Of the 96 313 patients hospitalised for COVID-19, 336 (0.35%) were subsequently admitted for self-harm within 12 months, compared to 20 135 (0.72%) of 2 797 775 patients admitted for other reasons. This difference remained significant after adjusting for sociodemographic factors (adjusted odds ratio (aOR) = 0.66, 95% CI: 0.59–0.73), psychiatric disorder history (aOR = 0.65, 95% CI: 0.58–0.73) and the level of care received during the initial hospital stay (aOR = 0.70, 95% CI: 0.63–0.78). History of psychiatric disorders and intensive care were strongly correlated with increased risk, while older age was inversely associated with self-harm admissions. Conclusions Hospitalisation for COVID-19 during the early pandemic was linked to a lower risk of subsequent self-harm than hospitalisation for other reasons. Clinicians should consider psychiatric history and intensive care factors in evaluating the risk of future suicide.

Aedes albopictus mosquitoes face numerous anthropic stressors in urban areas. These xenobiotics not only impact mosquito physiology but also shape the composition of their microbiota, which play important roles in host physiological traits. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants known to alter mosquito metabolism, but no studies have yet investigated their impact on microbiota. Using a bespoke indoor mesocosm tailored for Ae. albopictus mosquitoes, we investigated the dynamics of bacterial communities in both mosquitoes and their larval breeding sites following chronic exposure to a cocktail of PAHs consisting of benzo[a]pyrene, benz[a]anthracene, chrysene and benzo[b]fluoranthene. Our findings showed that PAHs have a stage-specific effect on mosquito microbiota, with a higher impact in larvae than in adults, contributing to 12.5 % and 4.5 % of the PAHs-induced variations, respectively. The presence of PAHs in the treated mesocosm led to the enrichment of bacterial families and genera known for their ability to catabolize PAHs, such as Comamonadaceae and Raoultella (increasing from 19 % to 30 % and from 1.2 % to 5.6 %, respectively). Conversely, prevalent taxa found in mosquito microbiota like Wolbachia and Cedecea exhibited a reduction (decreasing from 4 % to 0.8 % and from 12.8 % to 6.4 %, respectively). This reduction could be attributed to the competitive advantage gained by PAH-degrading taxa, or it could reflect a direct sensitivity to PAH exposure. Overall, this indicates a shift in microbiota composition favoring bacteria that can thrive in a PAH-contaminated environment. PAHs persisted in the water of breeding sites only the first 45 days of the experiment. Benzo[a]pyrene and benzo[b]fluoranthene were more susceptible to bioaccumulation in larval tissues over time. Overall, this study enhances our understanding of the impact of pollution on mosquitoes and could facilitate future research on the importance of symbiosis in urban-dwelling insect disease vectors. Given the recent advancements in the generation of axenic (microbe-free) and gnotobiotic (mosquitoes with a defined or specific microbiota) mosquitoes, further studies are needed to explore how changes in microbiota composition could influence mosquito responses to pollution, particularly in relation to host fitness, immunity, and vector competence.

Abstract We recently developed an immuno-oncotherapy against human papillomavirus (HPV)-induced tumors based on a lentiviral vector encoding the Early E6 and E7 oncoproteins of HPV16 and HPV18 genotypes, namely “Lenti-HPV-07”. The robust and long-lasting anti-tumor efficacy of Lenti-HPV-07 is dependent on CD8+ T-cell induction and remodeling of the tumor microenvironment. Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. To longitudinally monitor the evolution of the T-cell repertoire generated after the prime, homologous or heterologous boost with Lenti-HPV-07, we tracked T-cell clonotypes by deep sequencing of T-Cell Receptor (TCR) variable β and α chain mRNA, applied to whole peripheral blood cells (PBL) and a T cell population specific of an immunodominant E7HPV16 epitope. We observed a hyper-expansion of clonotypes post prime, accompanied by increased frequencies of HPV-07-specific T cells. Additionally, there was a notable diversification of clonotypes post boost in whole PBL, but not in the E7HPV16-specific T cells. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.

Abstract The aim of this study is to evaluate the accuracy of outcome reporting after elective visceral surgery in a low volume district hospital. Outcome measurement as well as transparent reporting of surgical complications becomes more and more important. In the future, financial and personal resources may be distributed due to reported quality and thus, it is in the main interest of healthcare providers that outcome data are accurately collected. Between 10/2020 and 09/2021 postoperative complications during the hospitalisation were recorded using the Clavien–Dindo classification (CDC) and comprehensive complication index by residents of a surgical department in a district hospital. After one year of prospective data collection, data were retrospectively analyzed and re-evaluated for accuracy by senior consultant surgeons. In 575 patients undergoing elective general or visceral surgery interns and residents reported an overall rate of patients with complications of 7.3% (n = 42) during the hospitalization phase, whereas a rate of 18.3% (n = 105) was revealed after retrospective analysis by senior consultant surgeons. Thus, residents failed to report patients with postoperative complications in 60% of cases (63/105). In the 42 cases, in which complications were initially reported, the grading of complications was correct only in 33.3% of cases (n = 14). Complication grades that were most missed were CDC grade I and II. Quality of outcome measurement in a district hospital is poor if done by unexperienced residents and significantly underestimates the true complication rate. Outcome measurement must be done or supervised by experienced surgeons to ensure correct and reliable outcome data.

Abstract Cryptography is crucial in protecting sensitive information and ensuring secure transactions in a time when data security and privacy are major concerns. Traditional cryptography techniques, which depend on mathematical algorithms and secret keys, have historically protected against data breaches and illegal access. With the advent of quantum computers, traditional cryptography techniques are at risk. In this work, we present a cryptography idea using logical phi-bits, which are classical analogues of quantum bits (qubits) and are supported by driven acoustic metamaterials. The state of phi-bits displays superpositions similar to quantum bits, with complex amplitudes and phases. We present a representation of the state vector of single and multi-phi-bit systems. The state vector of multiple phi-bits system lies in a complex exponentially scaling Hilbert space and is used to encode information or messages. By changing the driving conditions of the metamaterial, the information can be encrypted with exceptional security and efficiency. We illustrate experimentally the practicality and effectiveness of encoding and encryption of a message using a 5 phi-bits system and emphasize the scalability of this approach to an N phi-bits system with the same processing time.

Purpose To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS).Methods This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups.Results Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients.Conclusion The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.

Abstract Background The incidence, causes and impact of diaphragm thickness evolution in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are unknown. Our study investigates its evolution during the first week of VA-ECMO and its relationship with sweep gas flow settings. Methods We conducted a prospective monocentric observational study in a 12-bed ICU in France, enrolling patients on the day of the VA-ECMO implantation. The diaphragm thickness and the diaphragm thickening fraction (as index of contractile activity, dTF; dTF 10% modification from baseline to the last measurement), early extubation role (

We report increased 18F-FDG uptake in the right posterior mediastinal region in a 70-year-old woman following the discovery of a mass in the aftermath of a bronchitis episode. We also report increased 18F-Choline uptake in the right posterior mediastinal region in a 66-year-old man with newly discovered prostate cancer, which may indicate the presence of mediastinal metastases. Both patients had a thoracic MRI showing an intense gadolinium enhancement in the same region, consistent with thoracic schwannomas, which were subsequently proven histologically. This case highlights that schwannoma is a diagnostic pitfall in both 18F-FDG and 18F-Choline PET/CT.

Summary: Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes. Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320. Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58–0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65–0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76–1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82–1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91–1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89–1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65–1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98–1.64]). Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death. Funding: There was no funding source for this study.

Summary: Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. Video abstract: Video abstract

Atopic dermatitis (AD) is the most common chronic inflammatory dermatitis in developed countries, and has a major impact on those affected. Little is known about AD in elderly patients. This prospective multicentre observational study described the clinical characteristics and burden of AD in elderly subjects ≥ 65 years, as well as the therapeutic options chosen for this population in routine care, and compared findings with those in young adults with AD

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

Neutrophils are the first immune cells to reach inflamed sites and contribute to the pathogenesis of chronic inflammatory skin diseases. Yet, little is known about the pattern of neutrophil infiltration in inflamed skin in vivo and the mechanisms mediating their recruitment. Here, we provide insight into the dynamics of neutrophil infiltration in skin in response to acute or repeated inflammatory stress, highlighting a novel keratinocyte- and keratin 17 (K17)-dependent mechanism that regulates neutrophil recruitment to inflamed skin. We used the phorbol ester TPA and UVB, alone or in combination, to induce sterile inflammation in mouse skin. A single TPA treatment results in a neutrophil influx in the dermis that peaks at 12 h and resolves within 24 h. A subsequent TPA treatment or a UVB challenge, when applied 24 h but not 48 h later, accelerates, amplifies, and prolongs neutrophil infiltration. This transient amplification response (TAR) is mediated by local signals in inflamed skin, can be recapitulated in ex vivo culture, and involves the K17-dependent sustainment of protein kinase Cα (PKCα) activity and release of chemoattractants by stressed keratinocytes. K17 binds RACK1, a scaffold protein essential for PKCα activity. The N-terminal head domain of K17 is crucial for its association with RACK1 and regulation of PKCα activity. Analysis of RNAseq data reveals a signature consistent with TAR and PKCα activation in inflammatory skin diseases. These findings uncover a novel, keratin-dependent mechanism that amplifies neutrophil recruitment in skin under stress, with direct implications for inflammatory skin disorders.

Abstract Background Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development. Methods To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing. Results Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS. Conclusions Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.

Suspended particulate matter (SPM) in lakes exerts strong impact on light propagation, aquatic ecosystem productivity, which co-varies with nutrients, heavy metal and micro-pollutant in waters. In lakes, SPM exerts strong absorption and backscattering, ultimately affects water leaving signals that can be detected by satellite sensors. Simple regression models based on specific band or hand ratios have been widely used for SPM estimate in the past with moderate accuracy. There are still rooms for model accuracy improvements, and machine learning models may solve the non-linear relationships between spectral variable and SPM in waters. We assembled more than 16,400 in situ measured SPM in lakes from six continents (excluding the Antarctica continent), of which 9640 samples were matched with Landsat overpasses within ±7 days. Seven machine learning algorithms and two simple regression methods (linear and partial least squares models) were used to estimate SPM in lakes and the performance were compared. To overcome the problem of imbalance datasets in regression, a Synthetic Minority Over-Sampling technique for regression with Gaussian Noise (SMOGN) was adopted in this study. Through comparison, we found that gradient boosting decision tree (GBDT), random forest (RF), and extreme gradient boosting (XGBoost) models demonstrated good spatiotemporal transferability with SMOGN processed dataset, and has potential to map SPM at different year with good quality of Landsat land surface reflectance images. In all the tested modeling approaches, the GBDT model has accurate calibration (n = 6428, R2 = 0.95, MAPE = 29.8%) from SPM collected in 2235 lakes across the world, and the validation (n = 3214, R2 = 0.84, MAPE = 38.8%) also exhibited stable performance. Further, the good performances were also exhibited by RF model with calibration (R2 = 0.93) and validation (R2 = 0.86, MAPE = 24.2%) datasets. We applied GBDT and RF models to map SPM of typical lakes, and satisfactory result was obtained. In addition, the GBDT model was evaluated by historical SPM measurements coincident with different Landsat sensors (L5-TM, L7-ETM+, and L8-OLI), thus the model has the potential to map SPM of lakes for monitoring temporal variations, and tracks lake water SPM dynamics in approximately the past four decades (1984–2021) since Landsat-5/TM was launched in 1984.

Abstract In this study, the impact of adding 10% or 20% torula yeast (PB TY10 and PB TY20) to a fishmeal‐free diet on digestibility and growth of juvenile rainbow trout was assessed. The yeast diets were compared with a plant‐only diet (PB) and a diet containing 20% fishmeal (FM). The apparent digestibility of dry matter, protein, energy, and ash of yeast in trout (~120 g) were 78.6%, 93.8%, 84.8%, and 48.7%, respectively. All PB diets had higher protein digestibility and PB TY20 had higher ash digestibility than the FM diet. To assess growth, trout (~44 g) were divided into triplicate tanks (30 per tank) and fed one of the four experimental diets for 12 weeks. The PB diet resulted in lower growth and daily feed intake (p

Snakes responsible for bites are rarely identified, resulting in a loss of information about snakebites from venomous species whose venom effects are poorly understood. A prospective clinical study including patients bitten by a snake was conducted in Cameroon between 2019 and 2021 to evaluate the efficacy and tolerability of a marketed polyvalent antivenom. Clinical presentation during the first 3 days of hospitalization was recorded following a standardized protocol. This ancillary study aimed to assess the frequency of bites by the different species encountered in Cameroon and to describe the symptoms of bites by formally identified species. Of the 447 patients included in the study, 159 (35.6%) brought the snake that caused the bite that was identified by a specialist. Out of these, 8 specimens could not be identified due to poor condition, 19 were non-venomous species, and 95 belonged to Echis romani—formerly E. ocellatus—species. The remaining 37 specimens included 2 Atheris squamigera, 12 Atractaspis spp., 2 Bitis arietans, 11 Causus maculatus, 1 Dendroaspis jamesoni, 1 Naja haje, 1 N. katiensis, 5 N. melanoleuca complex, and 2 N. nigricollis. Symptoms, severity of envenomation, and post-treatment course are described. Symptoms and severity of bites are consistent with cases described in the literature, but some specific features are highlighted.

Background: Basic life support (BLS) is the recognition of sudden cardiac arrest and activation of emergency response system, followed by cardiopulmonary resuscitation (CPR), and rapid defibrillation. Aim: Our study aimed to determine the level of awareness of the Lebanese University medical students and trainees on BLS, by assessing the association between knowledge, attitude, and practice on BLS, and between the demographic variables and KAP scores. Methods: This was a cross-sectional study including 330 medical students enrolled at Lebanese University, from year four of general medicine till year five of residency. An online survey was used to collect data about demographic characteristics, knowledge (K), attitudes (A), and practice (P) about BLS. Data was analyzed using SPSS version 25. Results: Participants were 52.7% females, 47.3% males, and their mean age was 24 ± 2 years. Of the 330 participants, 38.8% received formal training regarding BLS. Medical students had low knowledge (90%), moderate to good attitudes (71.5%), and low practice (93%) regarding BLS. Multiple linear regression showed that knowledge was positively associated with age (p = 0.001), knowledge and information regarding BLS (p = 0.016), and any formal training/workshop regarding BLS (p = 0.021). Attitude was positively associated with academic year (p = 0.002) and knowledge (p = 0.003). Practice was positively associated with age (p < 0.001) and knowledge (p < 0.001). Conclusion: Most Lebanese University medical students showed low knowledge, moderate to good attitudes, and low practice regarding BLS. We recommend that CPR/BLS should be a core competency across all health care professional programs.

Background/Objectives: Drugs exhibiting poor aqueous solubility present a challenge to efficient delivery to the site of action. Spanlastics (a nano, surfactant-based drug delivery system) have emerged as a powerful tool to improve solubility, bioavailability, and delivery to the site of action. This study aimed to better understand factors affecting the physicochemical properties of spanlastics, quantify their effects, and use them to enhance the bioavailability of famotidine (FMT), a model histamine H2 receptor antagonist (BCS class IV). Methods: FMT was incorporated into nano-spanlastics drug delivery system. The ethanol injection method, Box–Behnken design, and mathematical modeling were utilized to fabricate famotidine-loaded nano-spanlastics and optimize the formula. Spanlastics were characterized for their particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, compatibility of the excipients (using DSC), in vitro drug release, and in vivo pharmacokinetics. Results: Span 60 (the non-ionic surfactant) and tween 60 (the edge activator) gave rise to spanlastics with the best characteristics. The optimal spanlastic formulation exhibited small particle size (−30 mV). The entrapment efficiency and drug loading of the optimum formula assured its suitability for hydrophobic drug entrapment as well as practicability for use. DSC assured the compatibility of all formulation components. The drug release manifested a biphasic release pattern, resulting in a fast onset and sustained effect. Spanlastics also showed enhanced Cmax, AUC0–24, and bioavailability. Conclusions: Spanlastics manifested improved FMT dissolution, drug release characteristics, membrane permeation, and pharmacokinetic behavior.

Background: Previous works have shown that the expression of Class-II-Transactivator (CIITA) in tumor cells reduces the growth of glioblastoma (GB) in animal models, but immune effects cannot solely explain this. Here, we searched for immune-independent effects of CIITA on the proliferation of GB. Methods: Murine GL261 and human U87, GM2 and GM3 malignant glioma cells were transfected with CIITA. NSG (immunodeficient) and nude (athymic) mice were injected in the striatum with GL261-wildtype (-WT) and -CIITA, and tumor growth was assessed by immunohistology and luminescence reporter genes. Clonogenic, sphere-formation, and 3D Matrigel-based in vitro growth assays were performed to compare the growth of WT versus CIITA-expressing murine and human cells. Bulk RNA sequencing and RT2 qRT-PCR profiler arrays were performed on these four cell lines to assess RNA expression changes following CIITA transfection. Western blot analysis on several proliferation-associated proteins was performed. Results: The intracerebral growth of murine GL261-CIITA cells was drastically reduced both in immunodeficient and athymic mice. Tumor growth was reduced in vitro in three of the four cell types. RNA sequencing and RT2 profiler array experiments revealed a modulation of gene expression in the PI3-Akt, MAPK- and cell-cycle regulation pathways following CIITA overexpression. Western blot analysis showed an upregulation of p27 in the growth-inhibited cells following this treatment. PDGFR-beta was downregulated in all cells. We did not find consistent regulation of other proteins involved in GB proliferation. Conclusions: Proliferation is drastically reduced by CIITA in GB, both in vivo and in vitro, notably in association with p27-mediated inhibition of cell-cycle pathways.

CAR T cell therapy has been an effective treatment option for hematological malignancies. However, the therapeutic potential of CAR T cells can be reduced by several constraints, partly due to immunogenicity and toxicities. The lack of established workflows enabling thorough evaluation of new candidates, limits comprehensive CAR assessment. To improve the selection of lead CAR candidates, we established a stringent, multistep workflow based on specificity assessments, employing multiple assays and technologies. Moreover, we characterized a human FOLR1-directed CAR binding domain. Selection of binding domains was based on extensive specificity assessment by flow cytometry and imaging, to determine on-/off-target and off-tumor reactivity. CAR T cell functionality and specificity were assessed by high-throughput screening and advanced in vitro assays. Our validation strategy highlights that assays comprehensively characterizing CAR functionality and binding specificity complement each other. Thereby, critical specificity considerations can be addressed early in the development process to overcome current limitations for future CAR T cell therapies.

Objectives The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA).Design and setting The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study.Participants From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort).Outcomes Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model.Results Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080).Conclusion In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Background & Aims: Major bleeding events during orthotopic liver transplantation (OLT) are associated with poor outcomes. The proportion of this risk related to portal hypertension is unclear. Hepatic venous pressure gradient (HVPG) is the gold standard for estimating portal hypertension. The aim of this study was to analyze the ability of HVPG to predict intraoperative major bleeding events during OLT in patients with cirrhosis. Methods: We retrospectively analyzed a prospective database including all patients with cirrhosis who underwent OLT between 2010 and 2020 and had liver and right heart catheterizations as part of their pre-transplant assessment. The primary endpoint was the occurrence of an intraoperative major bleeding event. Results: The 468 included patients had a median HVPG of 17 mmHg [interquartile range, 13-22] and a median MELD on the day of OLT of 16 [11-24]. Intraoperative red blood cell transfusion was required in 72% of the patients (median 2 units transfused), with a median blood loss of 1,000 ml [575-1,500]. Major intraoperative bleeding occurred in 156 patients (33%) and was associated with HVPG, preoperative hemoglobin level, severity of cirrhosis at the time of OLT (MELD score, ascites, encephalopathy), hemostasis impairment (thrombocytopenia, lower fibrinogen levels), and complications of cirrhosis (sepsis, acute-on-chronic liver failure). By multivariable regression analysis with backward elimination, HVPG, preoperative hemoglobin level, MELD score, and tranexamic acid infusion were associated with the primary endpoint. Three categories of patients were identified according to HVPG: low-risk (HVPG

Abstract Background Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. Methods We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. Results The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0–27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00–1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32–3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. Conclusion Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality. Graphical Abstract

Abstract Most untapped high-enthalpy geothermal resources are blind, meaning lacking surface evidence of their existence. The first step in their discovery is to find evidence of hydrothermal activity. Here we apply an approach based on the geochemistry of cold waters, which allowed us to identify evidence of the existence of a hydrothermal system at Piton de la Fournaise volcano (Réunion Island), and constrain its location. This approach uses the concentrations in B, Li, SO4, F, Mo, P, V, As and HCO3 and the isotopic ratios δ13C and δ11B as geochemical markers of hydrothermal activity that can be used even in waters with extremely low ion content (Electrical conductivity

PurposeRenal replacement therapy (RRT) is used in hyperammonemia to reduce the concentration of ammonia in the blood. In the case of plasma hyperosmolarity, RRT can also rapidly decrease plasma osmolarity, which may increase cerebral edema in these patients and favor the occurrence of brain herniation.MethodsWe conducted a retrospective clinical study in a tertiary care university-affiliated hospital. All patients admitted in a Pediatric Intensive Care Unit (PICU), less than 18 years old with ammonemia >150 µmol/L and who underwent RRT between January 2015 and June 2023 were included. We collected data on plasma osmolarity levels, osmolar gap and blood ammonia levels before and during RRT.ResultsEleven patients were included (10 with acute liver failure and 1 with a urea cycle disorders). Their mean age was 36.2 months. Before RRT, the median highest measured osmolarity was 320 (305–324) mOsm/L, whereas the median calculated osmolarity was 303 (293–314) mOsm/L, corresponding to an osmolar gap of 14 mOsm/L. Ammonia blood level over 400 µmol/L are significantly associated with higher plasma osmolarity (P-Value

BackgroundMultiple chemical sensitivity (MCS) develops in response to repeated small-level chemical exposures or a major exposure in a subset of people, who then experience symptoms that can range from mild to debilitating when exposed to chemicals. The arrival of the COVID-19 pandemic and the stringent health measures put in place may have increased the burden for those living with MCS, as it became more challenging to avoid chemicals that trigger their condition. ObjectiveThis study aimed to better understand the lived experience of Canadians living with MCS during the first year of the COVID-19 pandemic. MethodsAn online questionnaire was created to ask participants to compare daily living during the pandemic to before March 11, 2020. Data were collected in January and February 2021. Three areas were investigated: (1) environmental exposures to chemical triggers from ambient air (pollution from industry, farming, and traffic) and indoor air (the smell of cleaning products, cooking odors, and smoke); (2) access to, and satisfaction with, health care visits; and (3) how people experiencing MCS rated contact with their social network. ResultsIn all, 119 Canadians who had lived with MCS for more than a year completed the questionnaire. The participant sample was mostly female (86.6%, n=103) and highly educated, with 57.1% (n=68) having a university degree. Slightly more than half (57.1%, n=68) were older than 55 years. McNemar chi-square and Wilcoxon signed rank tests were used to evaluate if there were statistically significant changes before (“prepandemic period”) and after (“postpandemic period”) March 11, 2020. Perceived exposure to pollution from a highway or a road was significantly decreased from the prepandemic to postpandemic period (z=–3.347; P

Abstract Identifying how aerosol particles interact with atmospheric water is critical to understand climate and precipitation. Ice‐nucleating particles (INP) trigger the formation of atmospheric ice crystals at higher temperatures than pure water. They are difficult to characterize because of their scarce occurrence, and variability, in the atmosphere, especially at temperatures above −20°C. It has been demonstrated that at these temperatures, biological aerosol particles can contribute significantly to INP number concentration. This study incorporates a series of offline, size‐segregated measurements of INPs collected at the Puy de Dôme station (PUY, 1,465 m a.s.l.) over a 6 month period from October to May, covering the transitions from autumn, winter, to spring. These measurements show a general trend of decreasing particle number concentrations during the winter months and higher concentration during autumn and spring. INP concentrations measured in the range of −5 and −18°C, had concentrations of 0.001 INP/Lair at the warmest temperatures, and between 0.01 and 0.1 INP/Lair at the coldest temperatures. The majority of INP measured at temperatures warmer than −15°C were heat labile, suggesting a biological or organic origin. The INP variability was compared with collocated aerosol physical and chemical properties, allowing us to associate highest INP concentrations with local and marine origins. Following these comparisons, we use aerosol total number concentration to develop a new parameterization. In addition, this parameterization is specifically optimized for warmer temperature INP measurements, and demonstrated a good performance when tested on independent data sets.

Summary: Methods for detecting proteins in small extracellular vesicles (sEVs) lack sensitivity and quantitative accuracy, missing clues about health and disease. Our study introduces the Nano-Extracellular Omics Sensing (NEXOS) platform, merging electrical (E-NEXOS) and optical detection (O-NEXOS). E-NEXOS determines the concentration of target sEV sub-types, and O-NEXOS quantifies the concentration of target protein epitopes (TEPs) on those TEVs. In this work, both technologies were compared to several sEV detection tools, showing superior detection limits for CD9+CD81+ and CD9+HER2+ sEVs. Furthermore, the additional information on TEVs and TEPs from bulk sEV samples, provided new phenotyping capabilities. We determined the average number of CD81 and HER2 proteins on CD9+ sEVs, a number which was later validated on spiked human plasma. These results highlight the compatibility of NEXOS with complex biofluids and, as importantly, hint at its many potential applications, ranging from basic research to the anticipated clinical translation of sEVs.