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Elexacaftor–tezacaftor–ivacaftor has been approved in Europe for people with cystic fibrosis with at least one F508del CFTRvariant. Additionally, it is approved by the US Food and Drug Administration (FDA) for people with cystic fibrosis with at least one of 177 rare variants. The aims of this study were to describe the clinical response to elexacaftor–tezacaftor–ivacaftor for people with cystic fibrosis without a F508del CFTRvariant in France and to determine CFTRvariant responsiveness to elexacaftor–tezacaftor–ivacaftor based on the observed clinical response.

Understanding the reasons for and consequences of bodyweight change in people living with HIV initiating antiretroviral therapy (ART) is crucial to optimising long-term health and wellbeing. We aimed to examine bodyweight trends and associated factors among individuals with well estimated dates of HIV-1 seroconversion.

Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival.

Basal Stem Rot (BSR) disease caused by Ganoderma boninensepathogen, is a significant disease in oil palm-producing countries. In Malaysia and Indonesia, the disease attacks on a massive scale in oil palm plantations. Various methods of assessment have been explored on the disease in oil palm plantations. However, none of the measures have yielded an absolute solution. Therefore, this research analysed BSR disease and the resulting plant physiology reaction through water use efficiency (WUE) in oil palm trees to provide a comprehensive understanding of both conditions. The study sought to evaluate WUE performance for mature oil palm trees in varying BSR disease severity and suggested a novel model assessment from WUE for BSR disease severity. Based on the overall result, the WUE parameters were affected by BSR severity in different levels, especially when being compared between healthy (T0) and affected (T1, T2, T3) categories. Secondly, the correlation between WUE with different variables, Photosynthetic Rate (Pr), Transpiration Rate (Tr), Temperature Leaf (TempL), Intercellular CO2Concentration (Ci), Stomata Conductance (gs), and Chlorophyll Content (F), for frond 9 and frond 17 corresponded to the BSR disease severity. By performing a correlation analysis, a high correlation (0.5 and −0.5) was observed between these variables in both frond levels except in the Chlorophyll Content (F) variables (positive low correlation). Thirdly, the variables that contributed significantly to the WUE performance in mature oil palm included Pr, Tr,and Ci. Specifically, Prwas the highest value in both frond levels while Trand Ci were inconsistent and ranked second and third place in different frond levels, respectively. Finally, the WUE model developed provides a significant result in BSR disease severity with RMSE (0.54–0.19, 0.48–0.32) for training and validation models respectively. The model order is sorted into Model 1, Model 2, Model 3, and Model 4 in ascending order based on the RMSE accuracy assessment.

Myosteatosis is a measure of skeletal muscle quality that is readily identifiable on computed tomography (CT). The effect of preoperative myosteatosis on outcomes after radical esophagectomy remains unclear. This study aimed to correlate the presence of myosteatosis on CT scan with perioperative morbidity, mortality, and survival outcomes after esophagectomy in an Australian population across 3 esophageal cancer centers.

Mise à jour des recommandations de prise en charge des tumeurs germinales du testicule.

Decontamination of the clinical working environment and reprocessing of reusable dental instruments and devices are key components of modern infection control. This narrative review, which is part of a special issue devoted to contemporary infection control practices, highlights the latest evidence and the potential role of emerging technologies. The underpinning concepts of environmental decontamination and reprocessing have remained unchanged for many years, and key principles such as cleaning before disinfection or sterilisation remain true to the present day. What has changed in recent years are the range of options available, most notably for no-touch decontamination as an adjunct to regular environmental cleaning methods, including vapourised hydrogen peroxide, hydroxyl radicals, and ultraviolet C irradiation. In the realm of sterilisation, newer approaches include solar autoclaves and hydrogen peroxide gas plasma sterilisation. With all new and emerging technologies, greater attention is now being paid to safety as well as effectiveness, with stronger consideration of environmental impacts. This is especially relevant to the use of fully disposable surgical instruments vs reusable instruments. Because dental clinics have many configurations and sizes, each clinic needs to undertake local risk assessments to inform their decisions regarding suitable decontamination and reprocessing methods.

From early 2020 the COVID-19 pandemic drove dramatic increases in the production and use of single use disposable masks, respirators and gowns, and highlighted the vulnerability of supply chains for these items. This paper explores the impacts of the rising demands for these single use items through the lens of sustainability, by collating data on the carbon footprint and other impacts, and then discussing challenges, solutions, and future perspectives. Polypropylene and other key synthetic fibre components of these items are not biodegradable, and persist in the environments for prolonged periods generating microplastics as they degrade slowly. Various methods have been shown to allow limited repeated use of surgical masks and respirators, and this has spurred the development of masks and respirators designed for many cycles of reuse. Parallel discussions around gowns reveal that reuseable gowns offer many advantages for performance as well as reduced environmental impact. At the local dental clinic level, those making purchasing decisions should consider impacts of their product choices on the environment. Such impacts occur from manufacture, transport, and disposal of PPE, and from degradation within the environment. Regulators need to encourage use of reuseable items and facilitate this through local guidelines, while at the international level, more work is needed to develop uniform standards for reuseable masks, respirators and gowns.

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies.

Sin3 is an evolutionarily conserved repressor protein complex mainly associated with histone deacetylase (HDAC) activity. Many proteins are part of Sin3/HDAC complexes, and the function of most of these members remains poorly understood. SAP25, a previously identified Sin3A associated protein of 25 kDa, has been proposed to participate in regulating gene expression programs involved in the immune response but the exact mechanism of this regulation is unclear. SAP25 is not expressed in HEK293 cells, which hence serve as a natural knockout system to decipher the molecular functions uniquely carried out by this Sin3/HDAC subunit. Using molecular, proteomic, protein engineering, and interaction network approaches, we show that SAP25 interacts with distinct enzymatic and regulatory protein complexes in addition to Sin3/HDAC. Additional proteins uniquely recovered from the Halo-SAP25 pull-downs included the SCF E3 ubiquitin ligase complex SKP1/FBXO3/CUL1 and the ubiquitin carboxyl-terminal hydrolase 11 (USP11). Furthermore, mutational analysis demonstrates that distinct regions of SAP25 participate in its interaction with USP11, OGT/TETs, and SCF(FBXO3). These results suggest that SAP25 may function as an adaptor protein to coordinate the assembly of different enzymatic complexes to control Sin3/HDAC-mediated gene expression. The data were deposited with the MASSIVE repository with the identifiers MSV000093576 and MSV000093553.

Circulating proteomes provide a snapshot of the physiological state of a human organism responding to pathogenic challenges and drug interventions. The outcomes of patients with COVID-19 and acute respiratory distress syndrome triggered by the SARS-CoV2 virus remain uncertain. Tocilizumab is an anti-interleukin-6 treatment that exerts encouraging clinical activity by controlling the cytokine storm and improving respiratory distress in patients with COVID-19. We investigate the biological determinants of therapeutic outcomes after tocilizumab treatment. Overall, 28 patients hospitalized due to severe COVID-19 who were treated with tocilizumab intravenously were included in this study. Sera were collected before and after tocilizumab, and the patient’s outcome was evaluated until day 30 post-tocilizumab infusion for favorable therapeutic response to tocilizumab and mortality. Hyperreaction monitoring measurements by liquid chromatography–mass spectrometry-based proteomic analysis with data-independent acquisition quantified 510 proteins and 7019 peptides in the serum of patients. Alterations in the serum proteome reflect COVID-19 outcomes in patients treated with tocilizumab. Our results suggested that circulating proteins associated with the most significant prognostic impact belonged to the complement system, platelet degranulation, acute-phase proteins, and the Fc-epsilon receptor signaling pathway. Among these, upregulation of the complement system by activation of the classical pathway was associated with poor response to tocilizumab, and upregulation of Fc-epsilon receptor signaling was associated with lower mortality.

Les premières tentatives de transplantation de pancréas ont été réalisées dans la foulée des travaux d’Oscar Minkowski ayant démontré l’origine pancréatique du diabète en 1889. La première, attribuée à Williams en 1893, et toutes celles qui ont suivi jusqu’à ce que le traitement par l’insuline soit disponible en 1922, ont été des échecs. L’apparition de complications chroniques en dépit du traitement insulinique a relancé l’intérêt pour la transplantation. Les progrès techniques, la découverte du phénomène de rejet puis des groupes tissulaires par Jean Dausset ont marqué l’histoire de la transplantation du pancréas dont la première réussite est due à Richard Lillehei à Minneapolis en 1966. Les améliorations techniques proposées par Jean-Michel Dubernard à Lyon et les nouveaux médicaments immunosuppresseurs font de la transplantation pancréatique une solution à discuter chez les sujets diabétiques candidats à une transplantation rénale. La première greffe des îlots pancréatiques est réalisée en 1974 par David Sutherland à Minneapolis. En 2000, le protocole dit d’Edmonton favorise l’obtention de l’insulino-indépendance des sujets greffés. Dès 1997, le réseau franco-suisse GRAGIL développe des essais cliniques aboutissant en 2020 à l’autorisation de la greffe d’îlots en soins courants, seule ou associée à une transplantation rénale.

Nous rapportons les résultats de l’étude observationnelle, prospective, multicentrique de l’ETP diabète de type 2 (DT2) au sein de 33 Centres d’Examens de Santé (CES) de l’Assurance Maladie menée auprès de 5671 patients diabétiques de type 2 (dont 56 % en situation de vulnérabilité sociale selon le score EPICES), puis les résultats suite à la phase d’implémentation du programme dans 62 CES. L’expérimentation, conduite de 2008 à 2012, a permis d’apprécier la faisabilité de cette nouvelle offre dans les CES par l’évaluation de processus, ainsi que les effets et l’impact à 1 an du programme ETP-DT2. Une bonne adhésion au parcours a été observée, jusqu’à 6 mois, où des bénéfices perçus côté patients et médecins traitants ont été relevés. Après 1 an de suivi, 2913 patients diabétiques ont été revus au CES, parmi lesquels les principaux paramètres cliniques et paracliniques étaient significativement améliorés avec des bénéfices en termes de meilleur équilibre glycémique. Les résultats favorables ont conduit à l’implémentation du programme ETP-DT2 auprès de plus d’une soixantaine de centres ayant permis ainsi d’inclure en 2023 un total cumulé de 31 836 patients diabétiques, contribuant ainsi à une meilleure prise en charge des patients DT2 en situation de vulnérabilité sociale.

Background/Objectives: Giant cell arteritis (GCA) is an inflammatory vascular disease in which prompt and accurate diagnosis is critical. The efficacy of temporal artery biopsy (TAB) is limited by ‘skip’ lesions and a delay in histological analysis. This first-in-man ex-vivo study aims to assess the accuracy of optical frequency domain imaging (OFDI) in diagnosing GCA. Subjects/Methods: 29 TAB samples of patients with suspected GCA were submerged in 0.9% sodium chloride and an OFDI catheter was passed through the lumen to create cross-sectional images prior to histological analysis. The specimens were then preserved in formalin for histological examination. Mean intimal thickness (MIT) on OFDI was measured, and the presence of both multinucleate giant cells (MNGCs) and fragmentation of the internal elastic lamina (FIEL) was assessed and compared with histology, used as the diagnostic gold standard. Results: MIT in patients with/without histological evidence of GCA was 0.425 mm (±0.43) and 0.13 mm (±0.06) respectively compared with 0.215 mm (±0.09) and 0.135 mm (±0.07) on OFDI. MIT measured by OFDI was significantly higher in patients with histologically diagnosed arteritis compared to those without (p= 0.0195). For detecting FIEL and MNGCs, OFDI had a sensitivity of 75% and 28.6% and a specificity of 100% and 77.3% respectively. Applying diagnostic criteria of MIT > 0.20 mm, or the presence of MNGCs or FIEL, the sensitivity of detecting histological arteritis using OFDI was 91.4% and the specificity 94.1%. Conclusions: OFDI provided rapid imaging of TAB specimens achieving a diagnostic accuracy comparable to histological examination. In-vivo imaging may allow imaging of a longer arterial section.

Water quality has been found to significantly influence the flotation operations due to the alteration of surface properties of minerals. The effect of cations on the flotation of RE minerals has been studied, however, there are still very limited information regarding the effect of anions. The present study examined the impact of specific anions such as Cl−, SO42−, and HCO3−on the flotation performance of rare earth (RE) ore. This study integrates flotation experiments, rheology measurements, entrainment experiments, zeta potential measurements and settling experiments. It is observed that an increase in the concentration of these anions lead to a decrease in the recovery of RE minerals and an increase in the recovery of FeO minerals and thus negatively affecting flotation efficiency. This adverse effect is most pronounced with Cl−and least noticeable with HCO3−. An increase in the non-selective entrainment of gangue minerals is observed when the flotation pulp has higher viscosity. The reduction in the zeta potential of fine particles in the presence of these results in a higher pulp viscosity due to increased attractive forces between particles. These findings were verified by settling experiments and calculations based on the DLVO theory.

•Socio-aesthetics in a psychiatric department.•Interest in young patients.•Results in favour of practice.

Artificial intelligence (AI) can be seen to be at an inflexion point in India, a country which is keen to adopt and exploit new technologies, but needs to carefully consider how they do this. AI is usually deployed with good intentions, to unlock value and create opportunities for the people; however it does not come without its challenges. There are a set of ethical–social issues associated with AI, which include concerns around privacy, data protection, job displacement, historical bias and discrimination. Through a series of focus groups with knowledgeable people embedded in India and its culture, this research explores the ethical–societal changes and challenges that India now faces. Further, it investigates whether the principles and practices of responsible research and innovation (RRI) might provide a framework to help identify and deal with these issues. The results show that the areas in which RRI could offer scope to improve this outlook include education, policy and governance, legislation and regulation, and innovation and industry practices. Some significant challenges described by participants included: the lack of awareness of AI by the public as well as policy makers; India’s access and implementation of Western datasets, resulting in a lack of diversity, exacerbation of existing power asymmetries, increase in social inequality and the creation of bias; the potential replacement of jobs by AI. One option was to look at a hybrid approach, a mix of AI and humans, with expansion and upskilling of the current workforce. In terms of strategy, there seems to be a gap between the rhetoric of the government and what is seen on the ground, and therefore going forward there needs to be a much greater engagement with a wider audience of stakeholders.

Vascular malformations, which arise from anomalies in angiogenesis, encompass capillary, lymphatic, venous, arteriovenous, and mixed malformations, each affecting specific vessel types. Historically, therapeutic options such as sclerotherapy and surgery have shown limited efficacy in complicated malformations. Most vascular malformations stem from hereditary or somatic mutations akin to oncogenic alterations, activating the PI3K-AKT-mTOR, RAS-MAPK-ERK, and G-protein coupled receptor pathways. Recognizing the parallels with oncogenic mutations, we emphasize the potential of targeted molecular inhibitors in the treatment of vascular malformations by repurposing anticancer drugs. This review delves into the recent development and future use of such agents for the management of slow- and fast-flow vascular malformations, including in more specific situations, such as prenatal treatment and the management of associated coagulopathies.

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Biobased polylactide (PLA) films were modified with low reticulate polysiloxane gel acting as a scalable platform for the hydrophilization of polymeric film surface. The PLA thin film was first coated with poly(methylhydrogenosiloxane) (PMHS) by the sol–gel transition via the condensation of diethoxymethylsilane (DH) and triethoxysilane (TH) using trifluoromethanesulfonic acid as a catalyst. Then, hydrosilylation of Si–H bonds in the presence of Karstedt’s catalyst allowed the covalent grafting of hydrophilic alkene-containing molecules, i.e., triethylene glycol monomethyl allyl (TEGMEA) and a new zwitterionic allylcarboxybetaine (ACB) synthesized for the first time by the quaternization of dimethyl allyl amine (DMAA) with β-propiolactone. PMHS coating on the PLA film was evidenced by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The observation by atomic force microscopy (AFM) revealed a homogeneous coating with low roughness (RMS = 0.29 nm). The hydrophilicity of functionalized PLA films was determined by water contact angle (WCA) measurements using the captive bubble method. A large increase in wettability properties was observed for both grafting with TEGMEA (WCA = 38°) and ACB (WCA = 42°) in comparison with the native PLA film (WCA = 80°). Moreover, the biocompatibility and antifouling efficiency of functionalized PLA films were evaluated by protein adsorption, bacterial adhesion, and cytotoxicity tests. The results indicate that the grafting of the two types of hydrophilic compounds does not affect the biocompatibility of PLA while significantly reducing protein adsorption and bacterial adhesion, thus showing the great potential of this surface functionalization strategy for applications in the medical field.

Here, we report an improved synthesis of the bulky phosphanide anion [P(SiiPr3)2]−in synthetically useful yields and its complexation to group 12 metals. The ligand is obtained as the sodium salt NaP(SiiPr3)21in a 42% isolated yield and a single step from red phosphorus and sodium. This is a significantly higher-yielding and safer preparation compared to the previously reported synthesis of this ligand, and we have thus applied 1to the synthesis of the two-coordinate complexes M[P(SiiPr3)2]2(M = Zn, Cd, Hg). These group 12 complexes are all monomeric and with nonlinear P–M–P angles in the solid state, with DFT calculations suggesting that this bending is due to the steric demands of the ligand. Multinuclear NMR spectroscopy revealed complex second-order splitting patterns due to strong PP’ coupling. This work demonstrates that the synthesis of 1is viable and provides a springboard for the synthesis of low-coordinate complexes featuring this unusual bulky ligand.

Two-dimensional (2D) perovskites are well-known for the broad tunability of their optoelectronic properties. One of the prime methods is templating the inorganic sublattice via a selection of organic spacers. Here, with the use of magneto-optical spectroscopy, we demonstrate the remarkable potential of distortion engineering to tune the effective mass in 2D perovskites. We show that the 2D perovskites containing benzotriazole-based organic cations are characterized by the lowest reduced effective mass that has been measured for a lead iodide 2D perovskite. This stems directly from the very low degree of octahedral distortion in this material system. The practically flat structure of inorganic sublattice with no measurable out-of-plane corrugation results in the reduction of reduced effective mass by 12% with respect to the reference structure of (PEA)2PbI4. The reduction in the mass is naturally accompanied by a lower 1s exciton binding energy of ∼200 meV.

A new positive electrode material, Na2.85Mn0.4V1.6(PO4)2F2.4O0.6, is synthesized via a topochemical reaction in an ionic liquid medium, starting with a tailored precursor Mn0.2(VO)0.8PO4·2H2O. Its structural and chemical characterization was conducted using a comprehensive set of techniques including X-ray diffraction, X-ray absorption, and electron paramagnetic resonance spectroscopies, as well as inductively coupled plasma optical emission spectroscopy and electron probe microanalysis. These analyses not only allowed to determine the composition and structure but also shed light on the synthesis reaction mechanism. The resulting active material exhibits promising electrochemical performance, delivering a high capacity of 108 mA h/g at a rate of C/20 with an average potential of 3.75 V vs Na+/Na. Even at a higher rate of 1C, a specific capacity of 90 mA h/g is maintained and an excellent capacity retention of 94% is demonstrated after 200 cycles at C/5. In addition, XAS analysis conducted on materials recovered at different states of charge reveals the redox activity of both manganese and vanadium centers. More generally, this work showcases the feasibility of synthesizing stable Na-deficient polyanionic phases within the NazMnxV2–x(PO4)2F3–yOy(0 ≤ x, y≤ 2, and z≤ 3.6) material family.

ABSTRACTOver the past decade, new master-planned cities have been increasingly adopted worldwide as a strategy for economic growth. This paper reflects on new cities built from scratch as a field of study, and the particular methodological considerations associated with conducting research in and on new cities, structured around four key themes. First, we discuss the inherently global and transnational character of new cities as a specific challenge that shapes our approach to studying them. Second, we examine challenges of accessing people and information in rapidly developing private and high-profile ventures. Third, we address power dynamics and positionality in new city projects that are globally concentrated in “closed,” non-democratic contexts. Fourth, we draw attention to the unique logistical constraints and challenges of doing field research in new cities under construction and outline the disparate experiences of site visits, where varying degrees of control and surveillance impact research activities.